selective,covalent

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.

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.

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.

JAK3i is a selective covalent inhibitor of JAK3 kinase. JAK3i reveals two distinct temporal waves of STAT5 phosphorylation and more potently targets the second wave, which is required for cell cycle progression and T cell proliferation.

MS8511 HCl is a selective and potent covalent inhibitor of G9a/GLP that acts by targeting cysteine residues in the substrate binding site. MS8511 has anticancer activity and antiproliferative activity and reduces intracellular H3K9me2 levels.MS8511 can be used to study a wide range of cancers including brain, breast, and ovarian cancers .

Zongertinib is a human HER2-selective tyrosine kinase inhibitor, a novel TK that is highly selective for covalent binding to the HER2 tyrosine kinase domain (TKD).Zongertinib exhibits antitumor activity with inhibitory effects on pHER2 and EGF.

MS8511, a selective covalent irreversible inhibitor of G9a/GLP, targets a cysteine residue at the substrate binding site, displaying IC50 values of 100 nM (G9a) and 140 nM (GLP), alongside Kd values of 44 nM (G9a) and 46 nM (GLP). This compound effectively reduces cellular H3K9me2 levels and boosts antiproliferation activity, making it applicable in cancer research involving brain, breast, ovarian, lung, bladder, melanoma, and colorectal cancers, as well as studies on Alzheimer’s disease (AD), sickle cell disease, and Prader−Willi syndrome (PWS) [1].

MKK7-COV-9 is a selective and potent covalent inhibitor of MKK7 with inhibitory effects on MKK7-induced protein-protein interactions.MKK7-COV-9 interrupts the activation of primary B-cells in response to LPS.MKK7-COV-9 shows low cytotoxicity at high concentrations.

THZ1 (CDK7 inhibitor) is a novel selective and potent covalent CDK7 inhibitor.

ML-210 (CID 49766530) is a selective RAS and covalent glutathione peroxidase 4 (GPX4) inhibitor(GPX4, EC50 : 30 nM), with anti-cancer activity

FT671 is a non-covalent and selective inhibitor of USP7 (IC50: 52 nM) It also binds to the USP7 catalytic domain (Kd: 65 nM).

bio-THZ1 is a biotinylated version of THZ1. THZ1 is a selective and irreversibly covalent CDK7 inhibitor (IC50: 3.2 nM).

Psoromic acid is a selective and covalent rab-prenylation inhibitor targeting autoinhibited RabGGTase, it shows antibacterial activities against Streptococcus gordonii and Porphyromonas gingivalis, and it is an effective and safe natural drug plausible fo

MN551 is a potent inhibitor that targets the cysteine-directed electrophilic covalent activity essential for the function of SOCS2 within its CRL5 complex. This compound also acts as an E3 ligase mediator, facilitating PROTACs-induced selective protein degradation [1].

H3B-5942 belongs to a class of ERα antagonists referred to as selective estrogen receptor covalent antagonists (SERCA).

BBDDL2059 is a selective covalent inhibitor targeting EZH2, exhibiting an IC50 of 1.5 nM against the EZH2-Y641F mutant. It demonstrates potency in inhibiting lymphoma cell proliferation at nanomolar concentrations, proving its utility in anticancer research [1].

MRTX-1257 is a selective, irreversible, and covalent inhibitor of KRAS G12C. It has an IC50 of 900 pM for KRAS dependent ERK phosphorylation in H358 cells. MRTX1257 demonstrated 31% bioavailability in the mouse, with free fraction exposures well above the cellular potency In a PK/PD experiment, 77% target engagement.

CCG-273220 is a covalent inhibitor of G protein-coupled receptor (GPCR) kinase 5 (GRK5) (IC50: 220 nM).CCG-273220 covalently binds the GRK5 subfamily-specific residue Cys474 and is more selective for GRK5 than GRK2.

BTK inhibitor 19 is a highly selective, covalent BTK inhibitor ( IC 50 = 2.7 nM).

(S)-JDQ-443 is an isomer of JDQ-443 . JDQ-443 is an orally active, potent, selective, and covalent KRAS G12C inhibitor. JDQ-443 shows antitumor activity [1] [2] .

YKL-5-124 TFA, a potent and selective irreversible covalent inhibitor of CDK7, demonstrates IC50 values of 53.5 nM for CDK7 and 9.7 nM for the CDK7/Mat1/CycH complex. It exhibits over 100-fold selectivity for CDK7 over CDK9 and CDK2, while showing no activity against CDK12 and CDK13. This compound effectively induces cell-cycle arrest, inhibits E2F-driven gene expression, and has minimal impact on the phosphorylation status of RNA polymerase II.

YL5084, a covalent inhibitor selective for JNK2 and JNK3 over JNK1, demonstrates IC50 values of 70 nM and 84 nM for JNK2 and JNK3, respectively, compared to 2173 nM for JNK1. This compound also shows antiproliferative effects and induces apoptosis independently of JNK2 activity [1].

SB-435495 ditartrate is a potent, selective, reversible, non-covalent, and orally active inhibitor of Lp-PLA2, demonstrating an IC50 value of 0.06 nM [1] [3].

BTK-IN-8 is a potent, selective, peripheral covalent BTK inhibitor with an IC50 value of 0.22 nM and a Kd value of 0.91 nM. BTK-IN-8 exhibits good potency in whole blood CD69 cells with an IC50 value of 0.029 μM.

(R)-Pirtobrutinib ((R)-LOXO-305) is a less active enantiomer of Pirtobrutinib, and Pirtobrutinib is a highly selective and non-covalent next generation BTK inhibitor. Pirtobrutinib (LOXO-305) effectively inhibits diverse BTK C481 substitution mutations[1].

RMM-46 is a reversible and selective covalent inhibitor for MSK/RSK-family kinases.

Mevociclib (SY-1365) is a highly selective covalent inhibitor of CDK7. SY-1365 possesses therapeutic potential in both hematological and solid tumors.

LSD1-IN-18 is a potent, non-covalent, selective inhibitor of LSD1 (Ki:0.156 μM; KD: 0.075 μM).LSD1-IN-18 exhibited anti-proliferative effects in THP-1 leukemia cells and MDA-MB-231 breast cancer cells with IC50 (72 h) of 0.16 and 0.21 μM, respectively.

EN4 (EN4 MYC inhibitor) MYC inhibitor is a covalent ligand that targets cysteine 171 (C171) of MYC. It is selective for c-MYC over N-MYC and L-MYC, and inhibits MYC transcriptional activity, downregulates MYC targets, and impairs tumorigenesis.

FT827 is a covalent inhibitor of selective ubiquitin-specific protease 7 (USP7) (Ki=4.2 µM, Kd=7.8 µM) targeting the catalytic center of the autoinhibitory apolipoprotein form of USP7 for cancer research.

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.

AZD4625 (Compound 21) is a selective, potent, orally active, covalent and mutagenic mutant GTPaseKRASG12C inhibitor.

(R)-GSK-3685032 is the R-enantiomer of GSK-3685032. GSK-3685032 is a first-in-class, non-time-dependent, non-covalent, reversible, selective DNMT1 inhibitor with an IC 50 of 0.036 μM. GSK-3685032 induces robust loss of DNA methylation, transcriptional activation and inhibition of cancer cell growth.

2'-Thioadenosine (PD157432) serves as a selective and irreversible inhibitor of ErbB-1 and ErbB-2 tyrosine kinases, demonstrating an IC50 value of 45 µM against ErbB-2. It achieves covalent inactivation of ErbB-1 through modification of a cysteine residue within the enzyme's active site [1].

Rilzabrutinib (PRN1008) is a reversible covalent, selective and oral active inhibitor of Bruton’s Tyrosine Kinase (BTK)(IC50 of 1.3 nM).

PF 750 (ZINC27647189) is a selective and covalent inhibitor of FAAH. PF 750 shows IC50s varying from 16.2 to 595 nM in different incubation times.

EN40, as a covalent ligand, is a selective inhibitor of aldehyde dehydrogenase 3A1 (IC50: 2 uM).

Gunagratinib (ICP-192) is a potent and selective, orally active pan-FGFR (fibroblast growth factor receptors) inhibitor with low toxicity, exhibiting irreversible covalent binding to effectively inhibit FGFR activities. It is particularly suitable for cancer research purposes.

PPK-188, also known as CFT, is a novel selective covalent inhibitor of tryparedoxin (tpx), efficiently killing live african trypansosomes

UbcH5c-IN-1 is a selective small-molecule Ubiquitin-conjugating enzyme UbcH5c inhibitor (Kd: 283 nM for E2 UbcH5c-IN-1 by covalent binding with Cys85).

BTK inhibitor 18 is a selective, potent, covalent, orally active Btk inhibitor (IC50: 142 nM) that exhibits anti-inflammatory effects.

TX1-85-1 induces partial degradation of Her3 protein and attenuates Her3-dependent signaling. TX1-85-1 is an irreversible Her3 inhibitor (IC50: 23 nM). TX1-85-1 is also the first selective Her3 ligand, which forms a covalent bond with Cys721 located in th

LSD1-IN-19 (compound 29) is a selective, potent, non-covalent inhibitor of LSD1 (Ki: 0.108 μM, KD: 0.068 μM). The 72h IC50 values were 0.17 and 0.40 μM, respectively.

KRas G12R Inhibitor 1 (compound 3) is a selective covalent inhibitor targeting the KRas G12R mutation, leveraging the high nucleophilicity of mutant cysteines to bind irreversibly within the K-Ras Switch II region. This compound is utilized in cancer research [1].

SAR127303 is an effective covalent inhibitor of MAGL. SAR127303 behaves as a selective and competitive inhibitor of mouse and human MAGL.

EphB1-IN-10 is a potent and selective covalent inhibitor of receptor tyrosine kinase EphB1.

JS25 is a selective, covalent BTK inhibitor that deactivates BTK by chelating Tyr551, exhibiting an IC50 of 5.8 nM. It suppresses cancer cell proliferation, induces pronounced cell death, and enhances Burkitt's lymphoma murine xenograft model outcomes. Importantly, JS25 efficiently penetrates the blood-brain barrier.

Iadademstat dihydrochloride (ORY-1001(trans)) , a Potent and Selective Covalent KDM1A/LSD1 Inhibitor, for the Treatment of Acute Leukemia.

JH-X-119-01 is a highly potent and selective covalent inhibitor of IRAK-1.

SCP1-IN-1 (compound SH T-62) is a potent and selective covalent inhibitor against SCP1. SCP1-IN-1 promotes REST degradation and reduces transcriptional activity. In some glioblastoma cells, the high level of REST protein drives tumor growth. SCP1-IN-1 has the potential for the research of glioblastoma whose growth is driven by REST transcription activity [1].