non-covalent

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. BI-2865 showed antiproliferative activity on BaF3 cells expressing KRAS G12C, G12D or G12V mutants with an average IC50 value of approximately 140 nM.

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.

BI-4020 is a fourth-generation, orally active, and non-covalent inhibitor of EGFR tyrosine kinase. BI-4020 exhibits activity agains 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 exhibits high kinome selectivity and good DMPK properties.

GSK-3484862 is a non-covalent Dnmt1 inhibitor. It induces DNA hypomethylation to against cancer.

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

Samuraciclib hydrochloride (ICEC0942 hydrochloride) is a potent, selective, ATP competitive and oral active CDK7 inhibitor with IC50 of 41 nM. The selectivity of Samuraciclib hydrochloride is 45-, 15-, 230- and 30-fold higher than CDK1, CDK2 (IC50 is 578 nM), CDK5 and CDK9 respectively. Samuraciclib hydrochloride inhibits the growth of breast cancer cell lines with GI50 values between 0.2-0.3 μM. Samuraciclib hydrochloride has anti-tumor effects.

MAT-POS-e194df51-1 is an orally active, non-covalent, non-peptide inhibitor of the SARS-CoV-2 main protease (M^pro) with an IC_50 of 37nM. It exhibits cytotoxicity, with EC_50 values of 64nM in A549-ACE2-TMPRSS2 cells and 126nM in HeLa-ACE2 cells [1].

AMAS is a non-claevable heterobifunctional crosslinker with NHS ester and maleimide groups that enables covalent conjugation of amine- and sulfhydryl-containing molecules.

IA1-8H2, a non-covalent, non-competitive inhibitor of PHPT1 with an IC50 of 3.4 μM, is utilized in the study of lung cancer, hepatocarcinoma, and renal cancer [1].

SARS-CoV-2-IN-69 (Compound 7E) is a potent, non-covalent inhibitor of the SARS-CoV-2 main protease (M^pro) with an EC50 of 7.4 μM and also inhibits the papain-like protease (PL^pro) [1].

ARN19689 is an effective inhibitor of human NAAA, demonstrating high potency in the low nanomolar range (IC 50 = 0.042 μM). The compound acts through a non-covalent mechanism, highlighting its ability to interact with the enzyme for inhibition.

HECT E3-IN-1 (compound 3) is a HECT E3 ligase inhibitor that impedes Ub binding at the non-covalent Ub-binding site of Nedd4-1 [1].

SARS-CoV-2 3CLpro-IN-19 (Compound C5a), a non-covalent, non-peptide inhibitor of the SARS-CoV-2 3CLpro enzyme, exhibits potent in vitro activity with an IC50 of 0.7 μM. It demonstrates broad-spectrum efficacy against infection by Omicron subvariants (BA.5, BQ.1.1, and XBB.1.5) in human cells, with EC50 values ranging from 30-69 nM [1].

Avibactam sodium (NXL-104) dihydrate inhibits CTX-M-15 and β-lactamase TEM-1 with IC 50 s of 5 nM and 8 nM, respectively. Avibactam sodium dihydrate is a reversible and covalent inhibitor of non-β-lactam β-lactamase [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].

(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].

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.

CBR-470-1 is a potent inhibitor of glycolytic phosphoglycerate kinase 1 (PGK1) that activates NRF2 by increasing methylglyoxal levels. CBR-470-1 is a non-covalent Nrf2 activator with neuroprotective activity that protects SH-SY5Y neuronal cells from MPP+-induced cytotoxicity by activating the Keap1-Nrf2 cascade. cytotoxicity induced by MPP+.

GNE-6640 is a non-covalent inhibitor targeting ubiquitin specific peptidase 7 (USP7), exhibiting IC50 values of 0.75 μM for full-length USP7, 0.43 μM for the USP7 catalytic domain, 20.3 μM for full-length USP43, and 0.23 μM for Ub-MDM2, respectively.

GOT1 inhibitor-1 (GOT1 inhibitor 2c) is a novel, potent and non-covalent inhibitor of glutamate oxaloacetate transaminase 1 (GOT1) with an IC50 of 8.2 uM.

(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.

WU-04 is a non-covalent inhibitor targeting the 3CLpro protein of SARS-CoV-2, demonstrating high inhibitory effects on 3CLpro from six SARS-CoV-2 variants (Alpha, Beta, Gamma, Delta, Lambda, and Omicron) as well as two other coronaviruses (SARS-CoV and MERS-CoV) [1].

X77 is an effective non-covalent inhibitor of the main protease of SARS-CoV-2 ( SARS-CoV-2 M pro ) [1]. X77 binds to SARS-CoV-2 M pro with a Kd value of 0.057 μM [2].

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.

ZG1077, a covalent KRAS G12C inhibitor, is utilized in non-small cell lung cancer (NSCLC) research.

Proteasome-IN-4, a non-covalent proteasome inhibitor (IC 50 = 8.39 nM), exhibits potent antiproliferative effects on RPMI-8226, MM-1S, and MV-4-11 cell lines, making it valuable for cancer research.

EBL-3183, an indole-2-carboxylate, serves as a potent, reversible, non-covalent, and competitive inhibitor of metallo-β-lactamase (MBL), specifically targeting NDM-1 with a pIC50 of 7.7 [1].

Sulfo-SMPB sodium is a non-cleavable heterobifunctional chemical cross-linking reagent that combines N-hydroxysuccinimide ester and maleimide groups. This compound enables the covalent conjugation of molecules possessing amine and sulfhydryl functionalities.

Ensitrelvir (S-217622) fumarate is a novel orally active inhibitor, targeting the SARS-CoV-2 3CL protease (IC50 = 13 nM). It demonstrates non-covalent and non-peptidic characteristics. This compound represents a pioneering advancement in the development of effective antiviral agents against the SARS-CoV-2 virus.

Pirtobrutinib (LOXO-305) is an advanced BTK inhibitor that displays high selectivity and operates through a non-covalent mechanism. This compound effectively inhibits various BTK C481 substitution mutations, leading to tumor regression in BTK-dependent lymphoma tumors in mouse xenograft models. Furthermore, Pirtobrutinib exhibits remarkable selectivity for BTK, with more than a 300-fold difference compared to 370 other kinases tested. Notably, at a concentration of 1 μM, Pirtobrutinib demonstrates no significant inhibition of non-kinase off-targets.

JCN037 is potent, non-covalent and brain-penetrant inhibitor of EGFR(EGFR, p-wtEGFR and pEGFRvⅢ with IC50 of 2.49 nM, 3.95 nM, 4.48 nM , respectively).

MAGLi 432 is a potent, highly selective, non-covalent, reversible (MAGL) inhibitor that binds with high affinity to the MAGL active site, with IC50 values of 4.2 nM (human enzyme) and 3.1 nM (mouse enzyme), MAGLi 432 can be used to study neurological disorders such as chronic inflammation, multiple sclerosis, blood-brain barrier dysfunction, Alzheimer's disease and Parkinson's disease.

JBI-589 is an isoform-selective, non-covalent inhibitor of PAD4 that diminishes CXCR2 expression and impedes neutrophil chemotaxis. Additionally, it attenuates primary tumor growth and metastases, augmenting the efficacy of checkpoint inhibitors [1].

CDD-1819, a non-covalent and non-peptide compound, serves as a potent SARS-CoV-2 Mpro inhibitor, exhibiting a K i value of 5 nM. It also effectively inhibits the Mpro variants ΔP168, A173V, and ΔP168/A173V [1].

CDD-1733 is a potent, non-covalent, and non-peptide inhibitor of the SARS-CoV-2 main protease (Mpro) with an inhibition constant (K i) of 12 nM. It effectively inhibits Mpro variants including ΔP168, A173V, and the combined ΔP168/A173V [1].

JNJ-42226314 is a highly selective non-covalent monoacylglycerol lipase (MAGL) inhibitor with anti-injury effects.JNJ-42226314 shows efficacy via endogenous cannabinoid-2-acryloylglycerol (2-AG) in models of neuropathic pain and inflammatory pain.

MSA-2 dimer, a selective and orally active non-nucleotide STING agonist with a dissociation constant (Kd) of 145 μM, demonstrates prolonged antitumor and immunogenic activity. It non-covalently binds to STING as a dimer, showing greater permeability compared to cyclic dinucleotide[1].

DprE1-IN-4 is a potent, non-covalent inhibitor of DprE1 (IC50: 0.90 μg/mL). DprE1-IN-4 has acceptable pharmacokinetic properties and has a significant bactericidal effect in a mouse model of acute tuberculosis.

Hydroxy-α-sanshool is an alkyl amide isolated from the pepper. It acts as a TRPA1 covalent and TRPV1 non-covalent agonist (EC50s: 69 and 1.1 μM).

CDK12-IN-E9 is a potent and selective covalent CDK12 inhibitor and non-covalent CDK9 inhibitor while avoiding ABC transporter-mediated efflux. It has a weak binding ability to CDK7/CyclinH complex (IC50> 1 μM).

EGFR-IN-2 is a non-covalent, mutation-selective and irreversible second-generation EGFR inhibitor.

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

Antiviral agent 25 (compound 6g), a novel non-peptide analog covalent inhibitor of SARS-CoV-2 3CL pro, exhibits robust inhibitory activity against both SARS-CoV-2 3CL pro and SARS-CoV-2 PL pro, with IC50 values of 0.118 µM and 0.448 µM, respectively. Furthermore, it demonstrates significant antiviral effects against SARS-CoV-2, achieving an EC50 value of 7.249 µM [1].

Opnurasib (JDQ-443) is an orally available and selective and potent covalent KRAS G12C inhibitor with antitumor activity for the study of advanced non-small cell lung cancer.

Bisnorcymserine is a reversible inhibitor of butyrylcholinesterase. The leaving group, bisnoreseroline, interacts in a non-covalent way with Ser(200) and His(440), disrupting the existing interactions within the catalytic triad, and it stacks with Trp(84)

ZM223 hydrochloride is a potent, non-covalent, orally active inhibitor of NEDD8 activase (NAE).

Thailanstatin A is an ultra-potent inhibitor of eukaryotic RNA splicing (IC50 =650 nM). Thailanstatin A inhibits multiple cancer cell lines via non-covalent binding to the SF3b subunit of the U2 snRNA subcomplex of the spliceosome and shows low-nM to sub-nM IC 50 s against . Thailanstatin A, a payload for ADCs, is conjugated to the lysines on trastuzumab yielding “linker-less” ADC.

Salcaprozate sodium (SNAC), an oral absorption promoter, serves as a potent delivery agent for oral heparin and insulin by enhancing passive transcellular permeation through small intestinal epithelia. This is achieved through its capability to increase lipophilicity via non-covalent macromolecule complexation.

Avibactam (NXL-104) free acid is a covalent and reversible inhibitor of non-β-lactam β-lactamase (IC50s: 8 nM and 5 nM for β-lactamase TEM-1 and CTX-M-15).

(R)-FT671 is the R-isomer of FT671. FT671 is a potent, non-covalent and selective inhibitor of USP7 (IC50 of 52 nM)