Amirhossein Mafi

Table S1 from Microsatellite Instable Cancer Cells Acquire On-target Resistance Mutations to WRN Helicase Inhibitors

Faith C. Fowler, Jessica Gajda, Amirhossein Mafi, Aileen Kelly et autres

Summary of cellular and biochemical IC50 values for each WRN mutation and inhibitor.

Data from Microsatellite Instable Cancer Cells Acquire On-target Resistance Mutations to WRN Helicase Inhibitors

Faith C. Fowler, Jessica Gajda, Amirhossein Mafi, Aileen Kelly et autres

Abstract The Werner syndrome helicase (WRN) is a promising target for cancers with microsatellite instability (MSI), leading to the initiation of at least five phase I clinical trials. Acquired resistance is a substantial obstacle to obtaining lasting benefits from targeted therapies in …

Figure S5 from Microsatellite Instable Cancer Cells Acquire On-target Resistance Mutations to WRN Helicase Inhibitors

Faith C. Fowler, Jessica Gajda, Amirhossein Mafi, Aileen Kelly et autres

DNA unwinding activity of WRN mutant proteins

Table S2 from Microsatellite Instable Cancer Cells Acquire On-target Resistance Mutations to WRN Helicase Inhibitors

Faith C. Fowler, Jessica Gajda, Amirhossein Mafi, Aileen Kelly et autres

Summary of SPR data.

Figure S2 from Microsatellite Instable Cancer Cells Acquire On-target Resistance Mutations to WRN Helicase Inhibitors

Faith C. Fowler, Jessica Gajda, Amirhossein Mafi, Aileen Kelly et autres

Related to figure 2. (A) SPR sensorgrams of WRN WT and G729D treated with AC1 and AC2 (B) SPR sensorgram of WRN WT and D526_P530del treated with AC1 (C) Top: IGV browser window of whole exome sequencing variant calling file for AC1-resistant …

Figure S4 from Microsatellite Instable Cancer Cells Acquire On-target Resistance Mutations to WRN Helicase Inhibitors

Faith C. Fowler, Jessica Gajda, Amirhossein Mafi, Aileen Kelly et autres

Related to figure 4. (A) SPR sensorgram of WRN WT and F730L treated with AC1 (B) As in (A) with AC2 (C) As in (A) with C727R (D) SPR sensorgram of WRN WT and L528S treated with HRO761 (E) SPR sensorgram of …

Figure S1 from Microsatellite Instable Cancer Cells Acquire On-target Resistance Mutations to WRN Helicase Inhibitors

Faith C. Fowler, Jessica Gajda, Amirhossein Mafi, Aileen Kelly et autres

Related to figure 1. (A) SPR sensorgrams of WT WRN treated with AC1 and AC2. (B) DNA unwinding activity of wildtype WRN in the presence of AC1 and AC2. (C) Molecular docking of AC1 bound to the WRN helicase region (D) Viability …

Figure S3 from Microsatellite Instable Cancer Cells Acquire On-target Resistance Mutations to WRN Helicase Inhibitors

Faith C. Fowler, Jessica Gajda, Amirhossein Mafi, Aileen Kelly et autres

Related to figure 3. (A) Mean tumor volume measurements (± SEM) in a HRO71-resistant SW48 xenograft model treated with vehicle or 120 mg/kg HRO761 (n = 10 mice per treatment group). (B) Mean body weight of mice corresponding to figure 3A (C) …

Microsatellite Instable Cancer Cells Acquire On-target Resistance Mutations to WRN Helicase Inhibitors

Faith C. Fowler, Jessica Gajda, Amirhossein Mafi, Aileen Kelly et autres

The Werner syndrome helicase (WRN) is a promising target for cancers with microsatellite instability (MSI), leading to the initiation of at least five phase I clinical trials. Acquired resistance is a substantial obstacle to obtaining lasting benefits from targeted therapies in oncology …

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Systematic metabolite screening identifies functional regulators of the adenosine A2A receptor

Prashant Rao, Manoj K Rathinaswamy, Michelle M. Y. Chan, Chirag H. Patel et autres

The adenosine A2A receptor (A2AR) is a Class A G protein-coupled receptor (GPCR) that regulates inflammation, glucose metabolism, and energy homeostasis in metabolically active tissues. While the effects of small-molecule ligands and protein interactions with A2AR have been extensively studied, the regulatory …

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Mechanistic insights into a heterobifunctional degrader-induced PTPN2/N1 complex

Qi Hao, Manoj K Rathinaswamy, Kelly L. Klinge, Matthew A. Bratkowski et autres

PTPN2 (protein tyrosine phosphatase non-receptor type 2, or TC-PTP) and PTPN1 are attractive immuno-oncology targets, with the deletion of Ptpn1 and Ptpn2 improving response to immunotherapy in disease models. Targeted protein degradation has emerged as a promising approach to drug challenging targets …

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Structural basis of MPL activation by thrombopoietin

Amirhossein Mafi, Matthew A. Bratkowski, Jiefei Geng, Alyssa Brito et autres

Myeloproliferative leukemia protein (MPL), also known as thrombopoietin (TPO) receptor, is a class I cytokine receptor that is expressed on hematopoietic progenitors, promoting growth and differentiation toward the megakaryocyte lineage and is critical for normal platelet production. Mutations in MPL, TPO, or …

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