conformation

Avapritinib (BLU-285) is a selective, highly potent, and orally active inhibitor of KIT and PDGFRA activation loop mutant kinases, targeting KIT D816V (IC50:0.27 nM) and PDGFRA D842V (IC50:0.24 nM), and attenuates the transport functions of ABCB1 and ABCG2. It binds to the active conformation of the kinases and exhibits antitumor activity.

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.

SR-717 is a cGAMP analog, a non-nucleoside STING agonist that induces a closed activation conformation of STING. SR-717 has antitumor activity and promotes activation of immune cells and cross-presentation of antigens.

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.

MK-8033 hydrochloride is an effective and orally active dual inhibitor of ATP competitive c-Met Ron, with 1 nM for c-Met and 7nM for Ron IC50. MK-8033 hydrochloride has a high affinity for activated kinase conformation, and is suitable for the study of breast cancer, bladder cancer, and non-small cell lung cancer (NSCLC).

FzM1, a negative allosteric modulator (NAM) of the Frizzled receptor FZD4, diminishes WNT5A-dependent WNT responsive element (WRE) activity (log EC50inh=−6.2) by binding to an allosteric site on intracellular loop 3 (ICL3) of FZD4. This interaction changes the receptor's conformation and inhibits the WNT β-catenin signaling pathway.

CBHcy is a dual-substrate analogue, a specific BHMT inhibitor that causes betaine-homocysteine S-methyltransferase (BHMT) to adopt the same conformation as the ternary complex, potentially inducing the development of cysteinemia.

(+)-ORM-10921 is a conformation of ORM-10921 and can be used in chemical synthesis studies.

NVS-PAK1-1 is a potent allosteric inhibitor of PAK1 with an IC 50 of 5 nM for dephosphorylated PAK1 and 6 nM for phosphorylated PAK1 as assessed. Inhibition is ATP-competitive, most likely due to indirect competition due to incompatibility of ATP binding with the DFG-out binding conformation of the allosteric compound. NVS-PAK1-1 has an IC50 of 270 nM against dephosphorylated PAK2 and 720 nM against phosphorylated PAK2 respectively [1].

M1002 is a hypoxia-inducible factor-2 (HIF-2) agonist that enhances the affinity of HIF-2alpha and ARNT for transcriptional activation. It alters the Tyr2 conformation of the HIF-2alpha PAS-B structural domain and acts synergistically with inhibitors of the prolyl hydroxylase structural domain (PHD).

Amylose is a polysaccharide composed of α-D-glucose units linked by α(1→4) glycosidic bonds, accounting for about 20% of the total amount of starch. Amylose spatial conformation curls into a helix and forms a blue complex with iodine, which is widely used in the food industry, and can be used in a variety of researches as a natural product and a biochemical reagent.

4-Phenoxybenzylamine inhibits the function of the NS3 protein by stabilizing an inactive conformation, with an IC50 of approximately 500 μM against HCV NS3 4a.

HPK1-IN-8 is an allosteric, inactive, conformation-selective triazolopyrimidine ketone HPK1 inhibitor.

11-cis Retinal is a chromophore that binds to opsin in the mammalian visual system as an inverse agonist forming the inactive conformation of rhodopsin. When 11-cis retinal absorbs a photon of light, it isomerizes to form all-trans retinal beginning the phototransduction cycle, which is the basis for mammalian vision. A G121L mutation in opsin allows 11-cis retinal to bind as a partial agonist and activate rhodopsin in the absence of light. In a moth model of carotenoid deficiency-induced low visual sensitivity, 11-cis retinal application to compound eyes restored visual sensitivity almost completely.

CP-31398 dihydrochloride is a p53 stabilizer which stabilizes the active conformation of p53 and promotes p53 activity in cancer cell lines with mutant or wild-type p53.

Simufilam dihydrochloride (PTI-125 dihydrochloride) is a low toxicity, orally active filamin A (FLNA) activator, which can be used for the research of Alzheimer's disease. Simufilam dihydrochloride preferentially binds altered FLNA and restores its native conformation, restoring receptor and synaptic activities and reducing its α7nAChR TLR4 associations and downstream pathologies.

CK-666 is a cell-permeable inhibitor of the actin-related protein Arp2 3 complex, binding to and stabilizing its inactive state, thereby preventing the movement of the Arp2 and Arp3 subunits into the activated filament-like (short pitch) configuration.

PIN1 inhibitor API-1 is a specific Pin1 inhibitor (IC50: 72.3 nM) that retains the active conformation of pXPO5, restoring its ability to transport pre-miRNAs from the nucleus to the cytoplasm, thereby up-regulating anticancer miRNA biogenesis to suppress hepatocellular carcinoma development both in vitro and in vivo. PIN1 inhibitor API-1 directly and specifically binds to the Pin1 peptidyl-prolyl isomerase domain, effectively inhibiting Pin1 cis-trans isomerizing activity.

B-Raf IN 11 is a novel selective inhibitor. The DFG-in conformation of the B-Raf kinase V600E mutant is superior to the DFG-out conformation in colorectal cancer.

CP-31398 stabilizes the active conformation of p53 in cancer cells with either mutated or wild-type p53, enhancing its activity. Additionally, CP-31398 upregulates target genes of p53 such as p21WAF1 Cip1 and KILLER DR5. This compound possesses tumor-suppressive properties.

Cyrtominetin is an α-hemolysin inhibitor that works by directly binding to α-hemolysin and altering the conformation of its critical Loop region, subsequently inhibiting its lytic activity through a novel mechanism. This characteristic positions Cyrtominetin as a potential therapeutic agent against α-HL-mediated pathogenesis.

ACP6-12 is a ClpP activator and antibiotic. Its activity is over ten times greater than the initial compound ACP1-06. This enhanced activity has been confirmed by the co-crystal X-ray structure with ClpP, validating its predicted binding conformation. This evidence supports comparisons of how different ligand classes bind to the hydrophobic binding site.

MIRA-1 (WRN Helicase Inhibitor) is a restorer of wild-type p53 conformation cellular function and selectively inhibits Werner syndrome WRN helicase activity with an IC50 of 20 µM.

A 80915A is A semi-naphthoquinone antibiotic from Streptomyces aculeolatus. It is a potent inhibitor of gastric (H(+)-K+)-ATPase. Inhibition by A80915A is dependent on the conformation of gastric (H(+)-K+)-ATPase, potassium slows the rate of inhibition by