Small molecules frequently induce heterogeneous cell-death programs, complicating the mechanistic interpretation and optimization. Here, we investigate the ferroptotic and necrotic activities of the lethal small molecule CIL56 and related analogs. Although structurally similar, these compounds induce chemically separable death phenotypes. A phenotypic suppressor screen further identified distinct sets of small molecules that selectively attenuate ferroptotic or necrotic death. Classification of suppressor compounds based on shared ligand-based target predictions suggested nonoverlapping groups of candidate protein targets linked to each death modality. Together, these results show that integrating phenotypic screening with suppressor classification and target prediction can improve the interpretability of small-molecule phenotypic screens by prioritizing candidate proteins and pathways underlying the observed biological response.

Introduction: Hypereosinophilic syndrome (HES) is a group of rare diseases characterized by persistent hypereosinophilia in the blood and/or tissues, leading to organ damage and dysfunction. Biologics that target interleukin-5 (IL-5), such as benralizumab (an anti-IL-5 receptor alpha [anti-IL-5Rα] antibody) and mepolizumab (an anti-IL-5 antibody), could improve patient (pt) outcomes; however, real-world evidence of anti-IL-5/Rα treatment use in HES pts is limited. A systematic literature review and analysis of real-world case reports and cohort studies was conducted to understand real-world outcomes of pts receiving anti-IL-5/Rα treatment for HES. Methods: Searches to identify case reports and observational cohort studies were conducted in MEDLINE (via PubMed) and Embase, and supplemented with desktop searches using Google, to identify original articles (11/4/2015-10/31/2023) and conference abstracts (1/1/2021-10/31/2023) published in or translated to English. Other studies such as meta-analyses, clinical trials, and editorials were excluded. Selected publications were screened by up to three researchers, and included data on pts with HES and outcomes associated with anti-IL-5/Rα treatment. Where reported, study characteristics and data on pt demographics, clinical characteristics, treatments, and outcomes were collected for this descriptive analysis. The definition of improved organ involvement varied, but commonly included reported improvements in symptoms or laboratory test results. Results: In total, data were collected from 55 case reports (N=70) and five cohort studies (N=195): Kuang, 2018 (S1, N=35), Aalbers, 2022 (S2, N=15), Chen, 2022 (S3, N=123), Caminati, 2023 (S4, N=11), and Papajoannou, 2023 (S5, N=11). Of the pts from case reports, mean (standard deviation [SD]) age at diagnosis (n=68) was 38.5 (23.7) years, 40% (n=28/70) were female, and 67.2% (n=39/58) had idiopathic HES. Of the pts from cohort studies (N=195), median age ranged from 44-62 years, 33-63% were female, and 46-100% had idiopathic HES. Prior to initial anti-IL-5/Rα treatment (baseline) in case reports and cohort studies, HES manifestations were most common in dermatological (0-77%) and pulmonary (0-74%) systems. Overall, 46 pts started on benralizumab, and 211 pts started on mepolizumab, which is approved in HES. In case reports from baseline to post-initial anti-IL-5/Rα treatment, with a mean follow-up time of 39 weeks, mean (SD) blood eosinophil (bEOS) counts by treatment type were reduced from: overall (n=37), 7445 (15128) to 409 (1264) cells/µL (p=0.0066); benralizumab (n=10), 7410 (11866) to 58 (183) cells/µL (p=0.0824); mepolizumab (n=26), 7711 (16646) to 560 (1486) cells/µL (p=0.0340). After initial anti-IL-5/Rα treatment, bEOS counts in pts from cohort studies (reported in S1, S4, and S5 only) were reduced by 53-100% over 12-48 weeks. In case reports, 55.1% of pts (n=38/69) had improved organ involvement and nearly all pts (n=69/70) had improved symptoms after initiating anti-IL-5/Rα treatment; improved organ involvement was most common in renal (67%) and neurological (40%) systems. In cohort studies, HES organ involvement data after initiating anti-IL-5/Rα treatment were reported in S2 and S3 only. In S2 (N=15), 87% of pts on benralizumab experienced clinically relevant improvement in organ function after 22 months. For pts in S3 on mepolizumab (n=103) and benralizumab (n=15), 60% and 67% of pts, respectively, experienced an overall improvement in HES organ involvement. In cohort studies that reported disease flares (S1, S2, S4, and S5 only), the majority of pts receiving mepolizumab or benralizumab had no or reduced HES flares, including asthma flares. One pt from S2 on benralizumab stopped treatment due to refractory disease. In S1, pts on mepolizumab alone had significantly fewer mean flares per year (0.19) versus pts on conventional treatment (7.03) or mepolizumab plus another treatment (0.96; p<0.05). In pts from case reports, five had hematological relapse and 13 had HES flares, including 12 pts on mepolizumab (n=54) and one pt on benralizumab (n=13). Oral corticosteroid (OCS) dose was reduced by ≥50% in 41% of pts from case reports, and in 50-100% of pts from cohort studies. Conclusion: Use of anti-IL-5/Rα treatments in pts with HES is associated with significantly reduced bEOS counts, improved HES organ manifestations and symptoms, fewer HES flares, and reduced OCS dose.

Aim: To compare the effectiveness of in-class transition to all-oral ixazomib-lenalidomide-dexamethasone (IRd) following parenteral bortezomib (V)-based induction versus continued V-based therapy in US oncology clinics. Patients & methods: Non-transplant eligible patients with newly diagnosed multiple myeloma (MM) receiving in-class transition to IRd (N = 100; US MM-6), or V-based therapy (N = 111; INSIGHT MM). Results: Following inverse probability of treatment weighting, overall response rate was 73.2% with IRd versus 57.5% with V-based therapy (p < 0.0001). Median duration of treatment was 10.8 versus 5.3 months (p < 0.0001). Overall, 18/24% of patients discontinued IRd/V-based therapy due to adverse events. Conclusion: IRd after V-based induction was associated with significantly improved overall response rate and duration of treatment than continued V-based combination therapy. Clinical Trial Registration: US MM-6: NCT03173092; INSIGHT MM: NCT02761187 (ClinicalTrials.gov).

Patients with metastatic triple-negative breast cancer (mTNBC) have poor prognosis and limited treatment options. Sacituzumab govitecan (SG), a Trop-2–directed antibody–drug conjugate, is approved for patients with mTNBC who have received ≥ 2 systemic therapies (≥ 1 in the metastatic setting) based on the ASCENT study (NCT02574455). The current study describes real-world SG use and outcomes in patients with mTNBC in the United States. This retrospective, observational study included adult patients with mTNBC from the ConcertAI Patient360™ database who received SG in the second line (2L) and later from April 2020 to May 2022. SG use patterns, effectiveness, and tolerability are described. This analysis included 230 patients (median age 60 years, 26

Background: Historically, the clinical characteristics and treatment pathways for patients with uterine fibroids and heavy menstrual bleeding have differed between White and Black women. Objective: To provide a contemporary comparison of patient characteristics and treatment patterns among White and Black women with uterine fibroids and heavy menstrual bleeding in the United States. Study Design: This retrospective cohort study included administrative claims data from 46,139 White and 17,297 Black women with uterine fibroids and heavy menstrual bleeding from the Optum Clinformatics database (January 2011–December 2020) and 7353 White and 16,776 Black women from the IBM MarketScan Multi-State Medicaid Insurance database (January 2010–December 2019). Patients were indexed at their initial uterine fibroid diagnosis claim and were required to have a claim for heavy menstrual bleeding and ≥12 months of continuous enrollment pre- and postindex. Patients were followed until the earliest of death, disenrollment, hysterectomy date, or end of study database. Outcomes were stratified by race and included patient demographics, clinical characteristics, pharmacologic treatment patterns, and surgeries/procedures. Pearson's Chi-square test for categorical variables and Student's t-test for continuous data were used to evaluate differences in baseline characteristics. Descriptive statistics were used to characterize treatment pathways for hormonal contraceptive use in women with ≥24 months of follow-up. Kaplan–Meier survival analysis was used to estimate time until hysterectomy, with log-rank testing to assess between-group differences. Results: The mean (standard deviation) duration of follow-up was 44.6 (27.9) and 41.0 (24.9) months in the commercial and Medicaid databases, respectively. Mean (standard deviation) age at uterine fibroid diagnosis was lower for Black than White women in both databases (commercial: 42.3 [6.5] vs 44.4 [6.3] years; P<.0001; Medicaid: 39.6 [7.1] years vs 40.2 [7.2] years; P<.0001). Anemia was more prevalent in Black vs White women in both databases (commercial: 5.9% [1028/17,297] vs 3.6% [1648/46,139]; P<.0001; Medicaid: 7.0% [1180/16,776] vs 4.5% [331/7353]; P<.0001). In the commercial database, approximately one-half of women had claims for ≥1 bulk symptom, with no significant differences between groups. In the Medicaid database, significantly more White than Black women had claims for bulk symptoms (77.0% [5665/7353] vs 68.4% [11,477/16,776]; P<.0001). Approximately 40% of all patients received hormonal drug therapies as initial treatment, most commonly hormonal contraceptives. However, discontinuation of hormonal contraceptive therapy was nearly universal, with one-half discontinuing within a median treatment duration of ∼5 months. Most women stopped treatment after 1 or 2 agents (commercial: White, 89.9% [9757/10,857]; Black, 90.0% [3594/3993]; Medicaid: White, 92.2% [1635/1773]; Black, 94.2% [4454/4726]). Hysterectomy was the most common procedure, and was more common among White vs Black women (commercial: 43.9% [20,235/46,139] vs 37.8% [6536/17,297]; Medicaid: 46.8% [3444/7353] vs 32.0% [5364/16,776]). Conclusions: Black women with UF-HMB were diagnosed at a younger age than White women, and White women had higher hysterectomy rates than Black women, representing a shift from earlier researched treatment patterns. Patients with UF-HMB were also highly reliant on hormonal contraceptives, followed by nearly universal therapeutic discontinuation.

Abstract Recent approval of the HIF-2α antagonist belzutifan (Welireg) for patients with VHL disease has enabled the clinical opportunity to target the HIF-2 axis in cancer. This is particularly important for patients with clear cell renal cell carcinoma (ccRCC), in which 90% of tumors are VHL deficient, and approximately one in four primary tumors express HIF-2α exclusively. Clinical studies to date suggest an overall response rate (ORR) of 20-25% for belzutifan monotherapy, highlighting the need for a rational combination strategy to improve patient outcomes. This has led to multiple clinical trials testing belzutifan in combination with diverse therapeutic agents, including immune-checkpoint inhibitors, VEGFR-TKIs, and CDK4/6 inhibitors. HiberCell is developing a first-in-class GCN2 activator currently undergoing Ph1 clinical evaluation in patients with solid tumors (NCT05121948). GCN2 activation by HC-7366 drives the Integrated Stress Response (ISR), resulting in translation inhibition and delayed cell cycle progression in cancer cells. In preclinical studies, HC-7366 demonstrated significant antitumor activity associated with HIF suppression across diverse tumor models, including ccRCC (70% TGI), head and neck (33% regression), sarcoma (84% TGI) and prostate (100% TGI). Analysis of tumor samples revealed that HC-7366 inhibited both HIF-1α and HIF-2α, as well as multiple cell cycle regulators. Given the mechanistic link between HIF-2 and cell cycle regulation, and the noted combination benefit reported when CDK inhibitors are combined with belzutifan, we hypothesized that HC-7366 would enhance the antitumor effects of belzutifan in RCC. Combination studies in HIF-2 dependent 786-O and A-498 RCC xenografts demonstrated that HC-7366 improved the antitumor effects of belzutifan at clinically relevant doses. The combination of HC-7366 and belzutifan in A-498 drove robust tumor inhibition (~90% TGI). In 786-O, HC-7366 increased the number of complete responses from 2 of 8 tumors in the belzutifan-treated animals to 6 of 8 in the combination group. When tested in two belzutifan-resistant PDX models, HC-7366 resulted in significant monotherapy activity, achieving 17% regression as a maximal response, and inhibiting both HIF and cell cycle markers. Belzutifan is currently being tested in indications beyond RCC, so we evaluated the combination in VHLwt endometrial cancer model, MFE-280. Consistent with RCC models, the combination of HC-7366 and belzutifan resulted in tumor stasis with activation of ISR, enhanced inhibition of HIF and cell cycle markers in the combination vs belzutifan monotherapy. Together, these findings suggest that HC-7366 enhances belzutifan activity and serves as a rationale supporting clinical evaluation of this therapeutic combination. Citation Format: Michael E. Stokes, Feven Tameire, Paulina Wojnarowicz, Sho Fujisawa, Crissy Dudgeon, Sharon Huang, Nick Collette, Ben Harrison, Ashley LaCayo, Xiaohong Qiu, Takashi Kangas, Weiyu Zhang, Jeremy Drees, David Surguladze, Eric S. Lightcap, Nandita Bose. HC-7366, a potent GCN2 activator, complements belzutifan, a HIF-2⍺ antagonist, by providing combination benefit in belzutifan-sensitive models and monotherapy activity in belzutifan-resistant models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4615.

ABSTRACT Preventing the onset of autoimmune type 1 diabetes (T1D) is feasible through pharmacological interventions that target molecular stress-responsive mechanisms. Cellular stresses, such as nutrient deficiency, viral infection, or unfolded proteins, trigger the integrated stress response (ISR), which curtails protein synthesis by phosphorylating eIF2α. In T1D, maladaptive unfolded protein response (UPR) in insulin-producing β cells renders these cells susceptible to autoimmunity. We show that inhibition of the eIF2α kinase PERK, a common component of the UPR and ISR, reverses the mRNA translation block in stressed human islets and delays the onset of diabetes, reduces islet inflammation, and preserves β cell mass in T1D-susceptible mice. Single-cell RNA sequencing of islets from PERK-inhibited mice shows reductions in the UPR and PERK signaling pathways and alterations in antigen processing and presentation pathways in β cells. Spatial proteomics of islets from these mice shows an increase in the immune checkpoint protein PD-L1 in β cells. Golgi membrane protein 1, whose levels increase following PERK inhibition in human islets and EndoC-βH1 human β cells, interacts with and stabilizes PD-L1. Collectively, our studies show that PERK activity enhances β cell immunogenicity, and inhibition of PERK may offer a strategy to prevent or delay the development of T1D.

RCC PDX model characterization and response to treatment.

Supplementary Table 5: Aqueous kinetic solubility, Caco-2 permeability, plasma protein binding and hepatocyte stability of HC4, HC19, HC28 and GSK-157

Supplementary Figure S1. (a) MCF10A cells were treated with DMSO, thapsigargin (0.2 µM) alone or in combination with PERK inhibitors (2 µM)for 24 h and assayed for GADD34 expression by RT-qPCR. N = 3 wells per group (left graph). E0771 cells were treated with DMSO, thapsigargin(0.1 µM) alone or in combination with PERK inhibitors (2 µM) for 16 h and assayed for GADD34 expression by RT-qPCR. N = 3 wells per group (rightgraph) ****, p <0.0001 by t-test. (b) Flow diagram of the steps followed for single cell gene expression analysis with C1 and Biomark HD Fluidigm. Atotal of 255 DCCs and 90 primary tumor (PT) cells were analyzed. (c) List of the genes analyzed by high-throughput qPCR. (d) (upper) Immunoblotshowing the inhibition of PERK phosphorylation (T982) by the PERK inhibitor HC4 (2 µM) in MCF10A-HER2 cells plated on low attachment platesand incubated with inhibitor for 24 h. (lower) Immunoblot showing inhibition of PERK phosphorylation by treatment with increasing doses of HC4,HC19, HC28 and GSK2656157 for 4 h upon incubation with ER stress inducer tunicamycin in HEK293 cells. (e) The PERK inhibitor HC4 sensitizesto low dose ER stress-induced cell death in vitro. HC4 dose-response viability curve (Cell Titer Blue, CTB) in MCF10A-HER2 cells, in the absence (-)or in the presence of stress (low dose thapsigargin, Tg 2 nM) after 48 h. Dashed line indicates IC50 (≈ 9 nM). (f) MCF10A-Fv2E-PERK cells in 2Dculture were treated daily with 2 nM AP20187 (AP), HC4 2 µM and combination and assayed for cell death (left) or protein expression (right) after 24h. (g) In vivo pharmacokinetic profile of HC4 in mouse plasma. Dashed lines indicate the different biochemical, cellular and in vitro viability IC50s. (h)Effect of HC4 on body weight in female BALB/c mice (7–8-week-old) females treated twice per day (BID) with HC4 at indicated concentrations. (i)Effect of HC4 on total bone marrow cells (in two lower limbs) in MMTV-HER2 females treated for 2 weeks (N=5 per group) (left graph); effect of HC4on total white blood cells in MMTV-HER2 females treated for 2 weeks (N=11 per group) (middle graph)

Refers to: Mullens W, Dauw J, Martens P, et al. Acetazolamide in acute decompensated heart failure with volume overload. N Engl J Med. 2022;387:1185–1195.

e18871 Background: HR+/HER2- mBC remains incurable, despite progress made with endocrine therapy (ET) + CDK4/6i in prolonging survival. After resistance to ET-based treatment, options are limited to CT and a decrease in survival is observed with every subsequent line of treatment received. This study describes real-world outcomes in pts with HR+/HER2- mBC initiating CT or previously treated with CT in the US. Methods: This retrospective, observational cohort study used the ConcertAI Patient360™ curated dataset of electronic medical record data from the US. Pts (≥18 years) diagnosed with HR+/HER2- mBC and initiating their first CT from January 2011 to June 2021 were included. Real-world outcomes were assessed for all pts who initiated treatment with a first CT, and those who were subsequently treated with a second, third, and fourth CT. Index date was defined as the CT start date of each systemic therapy line. Results: In total, 1545 pts met the eligibility criteria and were included for analysis. Pts were primarily female (99%) and White (76%); median age was 61 years (IQR, 52-69) and 68% had visceral metastases. Most pts (80%) were treated in a community setting and 41% received their first CT in 1L; 58% and 44% had prior exposure to ET and CDK4/6i in the mBC setting, respectively. The median time from mBC diagnosis to first CT was 12 months (IQR, 1.4-30.8). Among all pts included, 57%, 31% and 17% were subsequently treated with a second, third, and fourth CT, respectively, during the study period. Capecitabine and paclitaxel were the most used as the first (45% and 29%), second (35% and 30%), and third (25% and 22%) CT, while gemcitabine (22%) and eribulin (20%) were used most as fourth CT. Clinical outcomes assessed are summarized in the table. Median real-world overall survival (rwOS; 95% CI) from time of mBC diagnosis was 48.5 months (45.5-51.5). Median rwOS from first CT treatment start date was 23.3 months (21.3-25.4). In pretreated pts with 1, 2, or 3 prior lines of CT, median rwOS from each index date was 16.5 months (14.8-18.3), 11.8 months (10.4-13.1), and 9.1 months (7.3-11.2), respectively. Conclusions: Among pts with HR+/HER2- mBC in this analysis, CT choice and real-world clinical outcomes per systemic therapy line were comparable to existing literature. Outcomes decreased as pts advanced CT lines, indicating that in this setting the unmet need remains high. More efficacious treatment options are needed for ET-resistant, chemo-naïve pts and pts pretreated with CT with HR+/HER2- mBC. [Table: see text]

Supplementary Table 2: Enzymatic and cell based IC50 values related to PERK, ATF4 and GCN2

Abstract Anti-angiogenic agents form the backbone of standard of care for advanced clear cell renal cell carcinoma (ccRCC), but their clinical impact is limited by primary and secondary resistance mechanisms that remain a critical problem. Furthermore, the approvals for VEGFR-targeting receptor tyrosine kinase inhibitors (VEGFR-TKIs), cabozantinib in second-line, and tivozanib in third-line RCC patients were based on modest objective response rates and median progression-free survival. There is an urgent need for novel mechanisms that target adaptive tumor responses that drive resistance to these agents, as well as combination drug partners that improve outcomes for patients. As part of their mechanism, VEGFR-TKIs induce oxygen- and nutrient-deprivation that drives ER stress. Tumors can evade deleterious ER stress by activating PERK branch of the integrated stress response, which arrests global translation and restores homeostasis. We hypothesized that inhibiting PERK would enhance the anti-tumor activity of VEGFR-TKIs in vivo and tested this using HC-5404, a potent and selective PERK inhibitor currently in Ph1 clinical testing (NCT04834778). Here, we present preclinical evidence that supports combining HC-5404 with VEGFR-TKIs in ccRCC. We demonstrate that axitinib, cabozantinib, lenvatinib, and sunitinib all activate PERK in 786-O ccRCC xenografts in a dose-responsive manner. The addition of HC-5404 significantly enhanced the tumor growth inhibition (TGI) of VEGFR-TKIs across multiple ccRCC tumor models, resulting in tumor stasis or regression in combination groups. Expression profiling and IHC analysis of tumor sections revealed that HC-5404 enhanced the anti-angiogenic effects of axitinib and lenvatinib in 786-O tumors, highlighting the protective role of PERK in response to anti-angiogenics. To evaluate whether the combination treatments could benefit a diverse patient population, sensitivity to HC-5404 and axitinib was evaluated across a panel of patient-derived xenograft (PDX) models. This experiment confirmed widespread responsiveness to the combination treatment that in some cases achieved >50% tumor regression. As tumor progression on VEGFR-TKIs limits the success of these agents in the clinic, we evaluated the effect of adding HC-5404 to tumors that have previously progressed on axitinib. In this study, 786-O xenografts were treated with axitinib for 2-weeks and non-responders were rerandomized into groups of either single agent or combination of HC-5404 and axitinib. The combination treatment significantly improved TGI relative to either monotherapy, resulting in tumor regression of ~20%. Taken together, these findings highlight that by disrupting an adaptive stress response evoked by VEGFR-TKIs, HC-5404 presents a clinical opportunity to enhance the anti-tumor effects of well-established standard of care therapies in ccRCC. Citation Format: Michael E. Stokes, Veronica Calvo, Crissy Dudgeon, Sho Fujisawa, Sharon Huang, Leyi Shen, Nupur Ballal, Joe McGinley, David Liu, Mark J. Mulvihill, Alan C. Rigby, Nandita Bose, Eric S. Lightcap, David Surguladze. Inhibition of PERK by HC-5404 sensitizes clear cell renal cell carcinoma tumor models to anti-angiogenic tyrosine kinase inhibitors. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4010.

Supplementary Table 7: KINOMEscan™ screening comparison of HC4, HC19, HC28 and GSK-157 at concentrations of 0.1, 1.0 and 10 mM versus RIPK1, AURKB, AXL, EPHB6, FLT3, KIT and KIT (V599D), kinases potently engaged by GSK157

AbstractPurpose: Tumors activate protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK, also called EIF2AK3) in response to hypoxia and nutrient deprivation as a stress-mitigation strategy. Here, we tested the hypothesis that inhibiting PERK with HC-5404 enhances the antitumor efficacy of standard-of-care VEGF receptor tyrosine kinase inhibitors (VEGFR-TKI). Experimental Design: HC-5404 was characterized as a potent and selective PERK inhibitor, with favorable in vivo properties. Multiple renal cell carcinoma (RCC) tumor models were then cotreated with both HC-5404 and VEGFR-TKI in vivo, measuring tumor volume across time and evaluating tumor response by protein analysis and IHC. Results: VEGFR-TKI including axitinib, cabozantinib, lenvatinib, and sunitinib induce PERK activation in 786-O RCC xenografts. Cotreatment with HC-5404 inhibited PERK in tumors and significantly increased antitumor effects of VEGFR-TKI across multiple RCC models, resulting in tumor stasis or regression. Analysis of tumor sections revealed that HC-5404 enhanced the antiangiogenic effects of axitinib and lenvatinib by inhibiting both new vasculature and mature tumor blood vessels. Xenografts that progress on axitinib monotherapy remain sensitive to the combination treatment, resulting in ∼20% tumor regression in the combination group. When tested across a panel of 18 RCC patient-derived xenograft (PDX) models, the combination induced greater antitumor effects relative to monotherapies. In this single animal study, nine out of 18 models responded with ≥50% tumor regression from baseline in the combination group. Conclusions: By disrupting an adaptive stress response evoked by VEGFR-TKI, HC-5404 presents a clinical opportunity to improve the antitumor effects of well-established standard-of-care therapies in RCC.

In vivo characterization of HC-5404.

Complete KinomeScan results of HC-5404 assayed at 100, 1000, and 10000 nM.

Supplementary Table 3: KINOMEscan™ screening comparison of HC4, HC19, HC28 and GSK-157 at concentrations of 0.1, 1.0 and 10 mM versus other eif2a kinases