covalent

Adagrasib (MRTX849) is an orally active and selective covalent inhibitor of KRAS G12C. Adagrasib binds to the GDP state of the inactive conformation of KRAS G12C and inhibits KRAS and its downstream signaling. Adagrasib exhibits inhibitory activity against KRAS G12C mutant tumors.

Sotorasib (AMG-510) is an orally active and selective covalent inhibitor of KRAS G12C. Sotorasib binds to the GDP state of the inactive conformation of KRAS G12C and inhibits KRAS and its downstream signaling. Sotorasib exhibits inhibitory activity against KRAS G12C mutant tumors.

PACMA 31 is an irreversible and covalent inhibitor of protein disulfide isomerase (PDI) with an IC50 of 10 μM. PACMA 31 significantly suppresses ovarian tumor growth and exhibits tumor targeting ability.

Batabulin (T138067) is an antitumor compound that binds covalently and selectively to a subset of the β-tubulin isotypes, disrupting microtubule polymerization. This disruption affects cell morphology, induces cell-cycle arrest, and ultimately leads to apoptotic cell death.

MRTX-1257 is a selective, irreversible, and covalent inhibitor of KRAS G12C with an IC50 of 900 pM for KRAS-dependent ERK phosphorylation in H358 cells. MRTX-1257 demonstrated 31% bioavailability in the mouse, with free fraction exposures well above cellular potency, and 77% target engagement in a PK/PD experiment.

YKL-5-124, a potent, selective and covalent CDK7 inhibitor with an IC50 of 9.7 nM, 1300 nM and 3020 nM for CDK7 Mat1 CycH, CDK2 and CDK9 respectively, displays biochemical and cellular selectivity for CDK7 over CDK12 13.

ML-210 (CID 49766530) is a glutathione peroxidase 4 (GPX4) inhibitor (EC50=30 nM) that is covalent and selective. ML-210 has antitumor activity and induces ferroptosis.

JAK3 Covalent Inhibitor-1 is a compound characterized by its potent and selective inhibition of Janus kinase 3 (JAK3), possessing an IC50 of 11 nM and demonstrating a 246-fold selectivity compared to other JAKs.

ER covalent antagonist-1 (Compound 39D) acts as an antagonist of the estrogen receptor α (ERα). This compound inhibits the proliferation of ERα-positive MCF-7 cells with an IC50 of 0.98 μM, induces cell cycle arrest at the G0 G1 phase, and triggers apoptosis. Additionally, ER covalent antagonist-1 demonstrates antitumor activity in mouse models.

RMC-6236 is an orally effective and novel triple complex RAS (ON) MULTI inhibitor, which is a potent non covalent inhibitor of multiple RAS variants in GTP binding state. RMC-6236 has anti-tumor activity and can be used in research related to RAS driven tumors. With rich experience in compound synthesis, we can provide fast customized synthesis services for this product according to your research needs.

RMC-9805 is a novel, mutant-selective, covalent and oral KRASG12D (ON) inhibitor. A stable and high affinity triple complex is formed between RMC-9805, KRASG12D, and cyclophilin A, which inhibits signal transduction downstream of KRASG12D (ON) by disrupting its interaction with downstream effectors. RMC-9805 can induce cell apoptosis and promote tumor regression in preclinical KRASG12D tumor models. With rich experience in compound synthesis, we can provide fast customized synthesis services for this product according to your research needs.

MRTX1133 is a KRAS G12D inhibitor (KD=0.2 pM) that is potent, selective, and non-covalent. MRTX1133 exhibits inhibitory activity against KRAS G12D-mutated tumors, but not against KRAS wild-type tumors.

Gut restricted-7 (GR-7) is a covalent and orally active pan-bile salt hydrolase (BSH) inhibitor that reduces gut bacterial BSHs and decreases deconjugated bile acid levels in the feces of mice.

Leptomycin B (LMB) is a potent inhibitor of the nuclear export of proteins and is a potent antifungal antibiotic blocking the eukaryotic cell cycle. Leptomycin B inactivates CRM1 exportin 1 by covalent modification at a cysteine residue.

Thailanstatin A is an ultra-potent inhibitor of eukaryotic RNA splicing (IC50 = 650 nM). It inhibits multiple cancer cell lines via non-covalent binding to the SF3b subunit of the U2 snRNA subcomplex of the spliceosome, displaying low-nM to sub-nM IC50s. Thailanstatin A, as a payload for ADCs, is conjugated to the lysines on trastuzumab, yielding linker-less ADC.

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]

MSA-2 is an orally available non-nucleotide STING agonist. The non-covalent dimer of MSA-2 binds to STING with nanomolar affinity. It shows anti-tumor activity in syngeneic mouse tumor models, synergizes with anti-PD-1, stimulates tumor secretion of interferon-β, induces tumor regression, and has long-lasting anti-tumor immunity. [3]

ML162 is a covalent glutathione peroxidase 4 (GPX4) inhibitor that induces ferroptosis. ML162 has antitumor activity and selectively inhibits cell lines expressing mutant RAS oncogenes.

GSK3685032 is a non-covalent and selective DNMT1 inhibitor(IC50 = 36 nM). The inhibitory effect is time-independent and reversible. GSK3685032 induces loss of DNA methylation and transcriptional activation and inhibits cancer cell growth.

6RK73 is a covalent, irreversible, and specific UCHL1 inhibitor (IC50: 0.23 µM) with almost no inhibition of UCHL3 (IC50: 236 µM).

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.

BSH-IN-1 is a potent, covalent inhibitor of gut bacterial recombinant bile salt hydrolases (BSHs; IC50s: 108 nM for B. longum BSH and 427 nM for B. theta BSH).

GSK-3484862 is a non-covalent Dnmt1 inhibitor that induces DNA hypomethylation, offering potential therapeutic benefits against cancer.

RMM-46 is a reversible covalent inhibitor with high ligand efficiency and selectivity for MSK/RSK family kinases.