conformational

ML346 is a novel activator of Hsp70.

Giredestrant (GDC-9545) potently competes with estradiol for binding and induces a conformational change within the ER ligand binding domain. Giredestrant has anti-tumor activity. Giredestrant, a non-steroidal ER ligand, is an orally active and selective estrogen receptor (ER) antagonist.

CCG-1423, a selective RhoA pathway inhibitor, suppresses SRF-mediated transcription.

Sulfo-ara-F-NMN is an analogue of nicotinamide mononucleotide (NMN) with cellular permeability. Sulfo-ara-F-NMN was selective to activate SARM1 and inhibited CD38 with an IC50 of about 10 μM. Activation by Sulfo-ara-F-NMN to Z-48 or NMN, which has a higher cyclase activity, causes conformational changes in SARM1, resulting in cADPR production, NAD depletion, and non-apoptotic cell death.

SPEN-IN-1 binding suppresses histone H3K27 trimethylation and blocks initiation of X-chromosome inactivation. SPEN-IN-1 binding reduces the conformational space of RepA and displaces cognate interacting protein factors including PRC2 and SPEN.

Trapencaine is a newly synthesized carbamate type local anesthetic that induces conformational changes in sodium channels on hypertrophic cell membranes.

DL-Homocysteine thiolactone hydrochloride (DL-Homocysteinethiolactone hydrochloride) is a cysteine derivative that binds to and induces conformational changes in various plasma proteins, slowing coagulation and inducing oxidative stress. It decreases left ventricular systolic blood pressure and cardiac force and induces seizures in vivo.

Canocapavir (ZM-H1505R) is a novel orally available HBV coat protein modulator with antiviral activity that induces conformational changes in the linker region of the HBV core protein, and can be used for the treatment of hepatitis B virus.

ARS-1323-alkyne is a switch-II pocket (S-IIP) inhibitor and a conformational specific chemical reporter of KRASG12C nucleotide state in living cells.

Rp-cAMPS triethylammonium salt is a competitive inhibitor of cAMP-dependent protein kinases I and II, inhibiting cAMP-induced conformational changes to block PKA activation.

SMAP-2 is an orally bioavailable activator of phosphatase 2A (PP2A) which binds to the PP2A Aα scaffold subunit to drive conformational changes in PP2A. It inhibits the growth of KRAS-mutant lung cancers .

(S)-Gossypol acetic acid ((S)-(+)-Gossypol acetic acid) is a conformational isomer of Gossypol that acts as a BH3 mimic capable of binding Bcl-xL and Bcl-2 proteins, with the potential to induce apoptosis and inhibit cell growth.

XMU-MP-9, a bifunctional compound, targets the C2 domain of Nedd4-1 and the allosteric site of K-Ras. It enhances the interaction and induces conformational changes within the Nedd4-1/K-Ras complex. Furthermore, XMU-MP-9 facilitates the ubiquitination and degradation of various K-Ras mutants and inhibits the proliferation of cells with these mutants. This compound is useful in cancer research.

DDO-3733 is a conformational activator of Protein Phosphatase 5 (PP5) that functions independently of TRP, facilitating the dephosphorylation of downstream substrates.

TCF199, a conformational stabilizer, facilitates the interaction between the 14-3-3ζ/E R α peptide and the 14-3-3ζ/Chibby peptide, thereby stabilizing the 14-3-3/TAZ peptide complex. The dissociation constant (Kd) of TCF199 with the 14-3-3/TAZ complex is 122 μM.

TH9028 is an inhibitor targeting MTHFD1, MTHFD2, and MTHFD2L, with IC50 values against the human-derived targets of 0.5 nM (MTHFD1), 11 nM (MTHFD2), and 27 nM (MTHFD2L), respectively. This compound binds to the substrate-binding region of the target enzymes, forming hydrogen bonds and other interactions with key amino acid residues, while also inducing conformational changes in the loop 1 region of the enzyme. Functionally, TH9028 slows down the progression of replication forks, induces replication stress, causes cell cycle arrest at the S phase, promotes apoptosis, inhibits thymidine synthesis, and leads to the misincorporation of uracil into DNA. In acute myeloid leukemia and T-ALL cells, TH9028 exhibits antiproliferative activity, while its effects on non-transformed cells are relatively weak. Therefore, TH9028 can be used in research related to acute myeloid leukemia.

BChE-IN-35 (Azo-9) is an inhibitor of BChE. This compound exhibits dynamic cis/trans conformational changes, with the cis isomer preferentially binding to BChE. Additionally, BChE-IN-35 can be utilized in research on Alzheimer's disease (AD).

SARS-CoV-2 3CLpro-IN-26 (Compound (S,R)-4y) is a conformational inhibitor of SARS-CoV-2 3CLpro with an IC50 of 0.43 μM. It demonstrates good cellular permeability, being able to effectively cross the cell membrane following co-incubation with Vero-E6 cells.

ART899 is a potent and specific conformational inhibitor of DNA polymerase θ (Polθ). It specifically inhibits the MMEJ activity of Polθ with an IC50 of 180 nM. Additionally, ART899 selectively enhances the radiosensitivity of tumor cells and possesses a strong independent antitumor effect on cancer cells.

PZ-3022 is an orally active, conformational PanK activator that counteracts C3-CoA inhibition. In a mouse model of propionic acidemia, it elevates hepatic CoASH and C2-CoA levels while reducing C3-CoA, making it useful for studying mitochondrial defects in propionic acidemia.

p53 Activator 13 is an inhibitor of the 6mA methyltransferase CamA and acts as a p53 activator. It intercalates into the minor groove of DNA bound by CamA, inducing conformational changes that displace the catalytic domain from DNA and trigger DNA damage responses via p53 activation. p53 Activator 13 is applicable in cancer research.

PIN1degrader-1 (Compound 158H9) is an inhibitor of the peptidyl-prolyl cis-trans isomerase (Pin1), with an IC50 of 21.5 nM. It covalently binds to Cys113 on Pin1, inducing conformational changes that decrease the protein's stability and lead to proteasome-dependent degradation. PIN1degrader-1 also inhibits the viability of various cancer cells, making it useful for cancer research.

BJP-07-017-3 is an inhibitor of proline cis-trans isomerase (Pin1) with an IC50 of 9 nM. It forms a covalent bond with Cys113 of Pin1, inducing conformational changes that decrease its stability and lead to proteasome-dependent degradation.

CIM-834 is an orally active, selective inhibitor that targets the coronavirus membrane protein (M protein), exhibiting potent inhibition of viral assembly in both SARS-CoV-2 and SARS-CoV. It binds non-covalently to the short form of the M protein (Mshort), stabilizing it and preventing its conformational change to the long form (Mlong) necessary for virion assembly, thus blocking virus particle formation. CIM-834 holds potential for research in COVID-19 and other coronavirus infections.