wt-1 a-1

WT-1 A1 is an attractive target for immunotherapy in patients with pancreatic adenocarcinoma.

BI-2865 is a non-covalent pan-KRAS inhibitor.BI-2865 binds to KRAS WT, G12C, G12D, G12V, and G13D mutants with KD values of 6.9, 4.5, 32, 26, and 4.3 nM, respectively.BI-2865 showed antiproliferative activity in BaF3 cells expressing KRAS G12C, G12D, or G12V mutants[1] . BI-2865 showed antiproliferative activity on BaF3 cells expressing KRAS G12C, G12D or G12V mutants, with an average IC50 value of approximately 140 nM.[1]

BI-4020 is a fourth-generation, orally active, and non-covalent inhibitor of EGFR tyrosine kinase. It exhibits activity against the triple mutant EGFR del19 T790M C797S variant (IC50=0.2 nM in BaF3 cell lines), the double mutant EGFR del19 T790M and primary mutant EGFR del19 (IC50=1 nM), and EGFR wt (IC50=190 nM). BI-4020 also shows high kinome selectivity and good DMPK properties.

HIV-1 inhibitor-54 is a potent inhibitor of WT HIV-1 (strain IIIB) in MT-4 cells, demonstrating anti-HIV activity with an EC50 of 32 nM. [HIV-1 inhibitor-54 can be used to study viral infections.]

Sonrotoclax is a potent, orally active inhibitor of Bcl2, demonstrating effective cell-killing activity against a range of lymphoma and leukemia cell lines [1].

Mutant IDH1-IN-1 is a potent inhibitor of the mutant IDH1 R132 h, exhibiting an IC50 of less than 0.1 μM.

K-Ras-IN-1, a K-Ras inhibitor, is characterized by its chemical formula C20H19ClN4O2S and is also known as N-[(1S)-3-cyclopropyl-1-[(6-fluoro-1H-benzimidazol-2-yl)sulfanyl]-2-oxo-1-(phenylmethyl)propyl]-4-fluorobenzenesulfonamide (compound [18, dashboard 819041] in brackets).

GSK3532795 is a potent, orally active, second-generation HIV-1 maturation inhibitor (EC50s: 10.2, 1.9, 2.7, and 13 nM for HIV-1 WT(human serum), HIV-1 WT, HIV-1 V370A, and HIV-1 ΔV370).

MtbHU-IN-1 is a Mycobacterium tuberculosis nucleoid-associated protein HU (MtbHU)inhibitor(binding to WT MtbHU with a Kd of 98 nM).

T338C Src-IN-1 is a potent inhibitor of the mutant Src T338C, exhibiting an IC50 of 111 nM relative to WT c-Src (showing a 10-fold increase).

Islatravir (MK-8591) is an effective anti-HIV-1 agent. It acts as a nucleoside reverse transcriptase inhibitor (EC50s: 0.068 nM, 3.1 nM, and 0.15 nM for HIV-1 (WT), HIV-1 (M184V), HIV-1 (MDR), respectively).

RET-IN-1 is a RET kinase inhibitor with IC50 values of 1 nM for RET (WT), 7 nM for RET (V804M), and 101 nM for RET (G810R).

D-PheTrAP is a bisubstrate analog inhibitor of 1-deoxy-d-xylulose 5-phosphate synthase (DXPS). It inhibits Escherichia coli DXPS (EcDXPS) and Pseudomonas aeruginosa DXPS (PaDXPS) with IC50 values of 0.52 μM, 2.1 μM, 2.4 μM, and 1.7 μM for wild-type (WT) EcDXPS, EcA426E, WT PaDXPS, and PaE431A, respectively.

QZ2135 (compound 20) is a PROTAC degrader that specifically targets RET and exhibits antitumor activity in vivo within a Ba/F3-KIF5B-RET-G810C xenograft mouse model. The compound demonstrates degradation activity with DC50 values of 4.7 nM (WT), 17.2 nM (V804M), and 73.8 nM (G810C) when targeting KIF5B-RET. QZ2135 is composed of the target protein ligand (red part) RETligand-3, the E3 ligase ligand (blue part) Lenalidomide-F, and the PROTAC Linker (black part) 7-Iodohept-1-yne, wherein the target protein ligand combined with the linker forms the conjugate RETLigand-Linker Conjugate-1.

KIT/PDGFRA-IN-1 (compound 19) is an inhibitor targeting the stem cell growth factor receptor (KIT) and platelet-derived growth factor receptor alpha (PDGFRA). Its IC50 values are 2.3 µM for KIT-wt, 12 µM for KIT-D816H, 492 µM for KIT-T670I, 0.8 µM for PDGFRA-wt, 99.9 µM for PDGFRA-D842V, 42.3 µM for PDGFRA-T674I, and 4.3 µM for PDGFRA-G680R. The GR50 values for GIST-T1, T1-a-D842V, and GIST-48B cell lines (gastrointestinal stromal tumor cell lines with PDGFR and KIT mutations) are 12 nM, 8900 nM, and ≥10,000 nM, respectively.

ASTX295 is a selective mouse double minute 2 (MDM2) antagonist with an IC50 value of less than 1 nM. It specifically inhibits the interaction between MDM2 and p53, reactivating wild-type (WT) TP53, which subsequently induces the expression of related transcriptional targets, leading to cell death and cell cycle arrest. ASTX295 holds potential for research in lymphoid malignancies such as diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and T-cell lymphoma.

FLT3/IRAK4-IN-1 is a selective inhibitor of FLT3 and IRAK4, exhibiting significant activity against FLT3-WT (IC50= 1.95 nM), FLT3-D835Y (IC50= 3.22 nM), and IRAK4 (IC50= 53.72 nM). It demonstrates low cytotoxicity towards normal bone marrow cells, effectively promotes apoptosis, and has potential to overcome resistance. FLT3/IRAK4-IN-1 can be utilized in studies of acute myeloid leukemia (AML).

NNRT-IN-9 (Compound EG28) is a non-nucleoside reverse transcriptase inhibitor (NNRT). It demonstrates strong antiviral and resistance-fighting activity against wild-type (WT) and various clinically relevant mutant strains (E138K and K103N + Y181C) of HIV-1, with EC50 values of 55 nM, 67 nM, and 3910 nM, respectively. NNRT-IN-9 is applicable in acquired immunodeficiency syndrome (AIDS) research.

USP7-IN-18 (Compound X21) serves as a novel USP7 inhibitor by directly suppressing enzyme activity and modulating downstream pathways, including the newly identified PCLAF target. At concentrations of 0.25-1 μM for 24 hours, it exhibits inhibitory effects. USP7-IN-18 effectively reduces proliferation in leukemia (RS4;11) and colon cancer (MC38/CT26.WT) cells at 0.01-100 μM over 72 hours. It demonstrates high selectivity for USP7 at 2.5 μM within 0.5 hours, surpassing eight other deubiquitinating enzymes. SPR analysis shows that at 1.95-2000 nM for 3 minutes, the compound binds the catalytic domain of USP7 with a KD value of 4.9 μM.

Mutant IDH1-IN-7 is a highly selective inhibitor of Isocitrate Dehydrogenase 1 (IDH1) with R132H mutation (IC50 = 0.26 μM, Kd = 2.1 μM) and R132C mutation (IC50 = 1.1 μM). It does not inhibit wild-type IDH1, IDH2-wt, or IDH2R140Q. Moreover, Mutant IDH1-IN-7 reduces the production of 2-hydroxyglutarate (2-HG) in U87-MG R132H cells (EC50 = 0.55 μM) and exhibits moderate antiproliferative effects on U87-MG R132H and HT-1080 cells.

NNRT-IN-11 (14l) is a potent non-nucleoside reverse transcriptase (NNRT) inhibitor, exhibiting EC50 values ranging from 6.50 to 52.9 nM against both wild-type (WT) and a range of HIV-1 mutant strains. NNRT-IN-11 demonstrates antiviral properties.

Lifirafenib (Beigene-283) is a potent inhibitor of RAF family kinases and EGFR in biochemical assays with IC50 of 23, 29 and 495 nM for the recombinant BRAFV600E kinase domain, EGFR and EGFR T790M/L858R mutant respectively.

MRTX9768 hydrochloride is a potent, orally active PRMT5 inhibitor. MRTX9768 hydrochloride is a synthetic lethal-based inhibitor binding the PRMT5-MTA complex[1]. MRTX9768 inhibits SDMA and cell proliferation in HCT116 MTAP-del cells (SDMA IC50 3 nM; prolif. IC50 11 nM) with marked selectivity over HCT116 MTAP-WT cells (SDMA IC50 544 nM; prolif. IC50 861 nM)[1].MRTX9768 selectively targets MTAP/CDKN2A-deleted tumors[2][1]. In xenograft studies, oral administration of MRTX9768 demonstrates dose-dependent inhibition of SDMA in MTAP-del tumors, with less SDMA modulation observed in bone marrow[1]. [1]. Christopher R. Smith, et al. Abstract LB003: Fragment based discovery of MRTX9768, a synthetic lethal-based inhibitor designed to bind the PRMT5-MTA complex and selectively target MTAP/CDKN2A-deleted tumors. AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA.[2]. Yingqing Chen, et al. Targeting protein arginine methyltransferase 5 in cancers: Roles, inhibitors and mechanisms. Biomed Pharmacother. 2021 Oct 4;144:112252.

Pal-KTTKS is a lipidated pentapeptide consisting of a fragment of the type I collagen C-terminal propeptide conjugated to palmitic acid .1 It increases collagen production in human corneal and dermal fibroblasts when used at concentrations of 0.002, 0.004, and 0.008 wt%.2 Following topical administration, pal-KTTKS (50 μg/cm2) is found in the stratum corneum, epidermis, and dermis of isolated hairless mouse skin.1 It can self-assemble into flat tapes and extended fibrillar structures.3 Pal-KTTKS has been detected in anti-wrinkle creams.4 |1. Choi, Y.L., Park, E.J., Kim, E., et al. Dermal stability and in vitro skin permeation of collagen pentapeptides (KTTKS and palmitoyl-KTTKS). Biomol. Ther. (Seoul) 22(4), 321-327 (2014).|2. Jones, R.R., Castelletto, V., Connon, C.J., et al. Collagen stimulating effect of peptide amphiphile C16-KTTKS on human fibroblasts. Mol. Pharm. 10(3), 1063-1069 (2013).|3. Castelletto, V., Hamley, I.W., Whitehouse, C., et al. Self-assembly of palmitoyl lipopeptides used in skin care products. Langmuir 29(29), 9149-9155 (2013).|4. Chirita, R.-I., Chaimbbault, P., Archambault, J.-C., et al. Development of a LC-MS/MS method to monitor palmitoyl peptides content in anti-wrinkle cosmetics. Anal. Chim. Acta 641(1-2), 95-100 (2009).