conformation

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.

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.

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.

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.

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.

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.

Cyclotraxin B acetate is an antagonist of TrkB receptors; inhibits BDNF-induced TrkB activity (IC50 = 0.30 nM). Allosterically alters TrkB receptor conformation but does not alter BDNF binding. Prevents BDNF-induced cold allodynia in mice. Also shown to exhibit putative anxiolytic properties in mice.

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

SYR127063 (BDBM-92454) (BDBM92454) is a potent and selective HER2 inhibitor, binds to HER2 in a reactive conformation.

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).

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).

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.

YMU1 is a human thymidylate kinase (hTMPK) inhibitor. YMU1 stabilizes the conformation of ligand-induced degradation (LID) region of hTMPK and blocks the catalytic site or ATP-binding site.

Necrostatin-34 (2-{[3-cyano-4-(4-methylphenyl)-6-oxo-1,4) is a RIPK1 kinase inhibitor, stabilizing RIPK1 kinase in an inactive conformation by occupying a distinct binding pocket in the kinase domain.

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.

Fz7-21 ((Ac)-LPSDDLEFWCHVMY-NH2) is a peptide antagonist of FZD7 . It antagonises WNT3A-induced Wnt-β-catenin signalling in HEK293 expressing FZD7. Fz7-21 impairs Wnt/β-catenin signaling in HEK293 cells stimulated with exogenous WNT3A (IC50=100 nM) or transfected with a construct expressing WNT3A or WNT1. Fz7-21 also blocks WNT3A-mediated stabilization of β-catenin in mouse L cells (IC50=50 nM).

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.

(E Z)-IT-603 is a cell-permeable c-Rel inhibitor (IC50: 3μM) that directly and reversibly binds to c-Rel, altering its conformation and inhibiting its DNA binding and transcriptional activity.

Zalutumumab, a fully human IgG1 monoclonal antibody, exhibits high affinity for the epidermal growth factor receptor (EGFR), selectively targeting its domain III. It functions by inhibiting the binding of the epidermal growth factor (EGF) and obstructing the receptor's active conformation through steric hindrance. With EC50 values of 7 nM for its IgG and 19 nM for the Fab fragment, Zalutumumab demonstrates potent interaction capabilities. This compound is primarily utilized in cancer research [1] [2] [3].

Benzoquinoquinoxaline (BQQ) is a heterocyclic compound with an aminoalkyl side chain, preferentially binding to DNA triplex structures by intercalating between the bases to stabilize the triplex conformation. Conjugation of BQQ to 1,10-phenanthroline allows specific binding and cleavage of double-strand DNA at sites forming a triplex structure [1].

PK7088, a pyrazole-based peptide, selectively reactivates mutant p53 to a conformation with wild-type characteristics, demonstrating anticancer activity in oncological studies [1].

Simufilam (PTI-125) (hydrochloride) is an orally active filamin A (FLNA) activator with low toxicity that can be used in the Alzheimer's disease research. Simufilam (hydrochloride) preferentially binds to altered FLNA and restores its native conformation, restores receptor and synaptic activities, and reduces its a7nAChR/TLR4 associations and downstream pathologies [1].

Imatinib Impurity E is a specific impurity found in Imatinib, an orally available inhibitor of multiple tyrosine kinases, including BCR/ABL, v-Abl, PDGFR, and c-kit. Imatinib (STI571) operates by semi-competitively inhibiting enzyme activity; it binds adjacent to the ATP binding site, inducing a closed or self-inhibited conformation [1] [2] [3] [4]. Additionally, Imatinib acts as an inhibitor against SARS-CoV and MERS-CoV [5].

VA5 is an transamidase inhibitor by direct binding at the transamidase site. VA5 also inhibits GTP-binding activities. It interaction at the transamidase site locks the protein in the extended/open conformation to disorganize/inactivate the GTP binding/GT

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.

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

IKKß-IN-124 is an allosteric inhibitor of IκBα phosphorylation and NF-κB transcriptional activity through selective capture of the inactive conformation and hence blockade of IKKβ S177/S181 phosphorylation.

Eprenetapopt (PRIMA-1Met) restores wild-type conformation and function to mutant p53, and triggers apoptosis in tumor cells. PRIMA-1MET also targets the selenoprotein thioredoxin reductase 1 (TrxR1), a key regulator of cellular redox balance.

Rezatapopt (PC14586) is a small molecule p53 reactivator with anti-tumor activity that selectively binds to the cleft present in the TP53 Y220C mutant protein and restores the p53 wild-type (normal) conformation and transcriptional activity, and can be used to study locally advanced or metastatic solid tumors.

GNF-6 (Compound 14), an ATP competitive inhibitor, inhibits the gatekeeper threonine residue mutation of BCR-ABL-T315I with IC50 values of 0.25 μM for c-ABL-T334I, 0.09 μM for BCR-ABL, and 0.590 μM for BCR-ABL-T315I variants. It disrupts the assembly of the hydrophobic spine (a network of hydrophobic interactions), locking the kinase in an inactive 'DFG-out' conformation [1].

[Glu4]-Oxytocin is a suitable derivative of oxytocin for conducting a thorough investigation, utilizing various methods, into the conformation of oxytocin-like molecules in aqueous solution.

MBD, a novel fluorescent probe (7-(p-Methoxybenzylamino)-4-nitrobenz-2,1,3-oxadiazole), is utilized to study the conformation of protein and nucleoprotein. Its application is extended to bacterial ribosomes, as well as bovine trypsinogen and trypsin. MBD exhibits significant fluorescence when it binds to the hydrophobic region of macromolecules [1][2].

1. Epiberberine may be caused drug interactions based on CYP2D6 enzyme. 2. Epiberberine has anti-adipogenic effect is mediated by downregulation of the Raf MEK1 ERK1 2 and AMPKα Akt pathways during 3T3-L1 adipocyte differentiation. 3. Epiberberine, as the brightest FSA emitter among the alkaloids, can also serve as an efficient conformation probe for HTG DNA and discriminate the DNA G-quadruplex from the RNA counterpart.

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.

KALA, an amphiphilic peptide, adopts an α-helical conformation under physiological pH conditions. It functions as a fusogenic peptide, modifying the liposomal membrane that encapsulates plasmid DNA, thereby facilitating liver targeting and DNA transfection through galactose receptors.

J-31 is an inactive conformation inhibitor of ITK.

Simufilam (PTI-125) is a low toxicity, orally active filamin A ( FLNA ) activator. Simufilam preferentially binds altered FLNA and restores its native conformation, restores receptor and synaptic activities, reduces its a7nAChR/TLR4 associations and downstream pathologies. Simufilam can be used in Alzheimer's disease research[1].

RGD peptide (GRGDNP) (TFA) promote apoptosis through activation of conformation changes that enhance pro-caspase-3 activation and autoprocessing.

WAY-255348 is a potent nonsteroidal progesterone receptor (PR) antagonist. WAY-255348 inhibits the activity of progesterone. WAY-255348 achieves antagonist activity by binding to and subsequently preventing progesterone-induced nuclear accumulation, phosphorylation and promoter interactions of the PR. WAY-255348 bound PR conformation was similar to that of a progesterone agonist-bound PR and distinct from steroidal antagonist-bound PR conformations. WAY-255348 inhibits PR action through a novel molecular mechanism that is distinct from previously studied PR modulators and may be a useful tool to further understanding of PR signaling pathways.

PF-05381941 is a potent dual inhibitor of TAK1 p38α, exhibiting IC50 values of 156 nM and 186 nM, respectively[1].

Photoswitchable Kv channel blocker (IC50 values are 2 and 64 μM at 500 nm and 380 nm respectively). Switches conformation from cis to trans at 500 nm and trans to cis at 380 nm. Exhibits minimal activity at Nav1.2 and L-type Ca2+ channels. Stimulates action potential firing of hippocampal neurons in vitro at 500 nm and restores visual responsiveness in blind mice at 380 nm. Fortin et al (2008) Photochemical control of endogenous ion channels and cellular excitability. Nat.Methods 5 331 PMID:18311146 |Polosukhina et al (2012) Photochemical restoration of visual responses in blind mice. Neuron 75 271 PMID:22841312 |Banghart et al (2009) Photochromic blockers of voltage-gated potassium channels. Angew.Chem.Int.Ed. 48 9097 PMID:19882609

Lamin fragment has a peptide sequence of Lys-Ala-Gly-Gln-Val-Val-Thr-Ile-Trp. Lamin polypeptides have an almost complete α-helical conformation with multiple α-helical domains separated by non-α-helical linkers that are highly conserved in length and amin

Antagonist of TrkB receptors; inhibits BDNF-induced TrkB activity (IC50 = 0.30 nM). Allosterically alters TrkB receptor conformation but does not alter BDNF binding. Prevents BDNF-induced cold allodynia in mice. Also shown to exhibit putative anxiolytic p

SLMP53-2 is a mutant p53 reactivator that restores the wild-type-like conformation and DNA-binding ability of mutp53-Y220C through enhanced interaction with Hsp70, thereby reinstating p53's transcriptional activity. This compound induces cell cycle arrest, apoptosis, and endoplasmic reticulum (ER) stress, displaying antitumor activity [1] [2].

DC-Srci-6649 is a potent and selective inhibitor of c-Src kinase, effectively blocking its phosphorylation and stabilizing it in an inactive conformation.

MRGPRX1 agonist 4 is a potent and orally active Mas-related G protein-coupled receptor X1 (MRGPRX1) positive conformation modulator (EC50: 0.1 μM). MRGPRX1 agonist 4 ameliorated the behavioral thermal allergic response in mice, a model of MRGPRX1 neuropathic pain.

HPK1-IN-8 is an allosteric inhibitor that selectively targets the inactive conformation of full-length HPK1.

Epiberberine chloride, a natural pro-berberine from Coptis chinensis Franch. is an AChE, BChE, and BACE1 inhibitor with IC50 values of 1.07, 6.03, and 8.55 μM, respectively.Epiberberine chloride has antioxidant effects and inhibits the effects of Ca9-22 and Fa2R. Epiberberine chloride has antioxidant effects, inhibits the motility of Ca9-22 and FaDu cell lines, and can be used to study hyperlipidemia, Alzheimer's disease and diabetes.