MedChemexpress) New Small Molecules for April 2021
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2021-04-08
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LC-2 is a potent and first-in-class PROTAC capable of degrading endogenous KRAS G12C, with DC50s between 0.25 and 0.76 ¥ìM. LC-2 covalently binds KRAS G12C with a MRTX849 warhead and recruits the E3 ligase VHL, inducing rapid and sustained KRAS G12C degradation leading to suppression of MAPK signaling in both homozygous and heterozygous KRAS G12C cell lines.
TEI-9648, a Vitamin D3 Lactone analogue, is a potent and specific vitamin D receptor (VDR) antagonist. TEI-9648 inhibits VDR/VDRE-mediated genomic actions of 1¥á,25(OH)2D3. TEI-9648 also inhibits HL-60 cell differentiation induced by of 1¥á,25(OH)2D3. TEI-9648 has the potential for bone metabolism research.
GIP, human TFA, a peptide hormone consisting of 42 amino acids, is a stimulator of glucose-dependent insulin secretion and a weak inhibitor of gastric acid secretion. GIP, human TFA acts as an incretin hormone released from intestinal K cells in response to nutrient ingestion.
UFP-101 TFA is a potent, selective, and competitive antagonist of the N/OFQ peptide (NOP) receptor, with a pKi of 10.24. UFP-101 TFA displays >3000-fold selectivity over ¥ä, ¥ì and ¥ê opioid receptors. UFP-101 TFA shows antidepressant-like effect.
AES-135, a hydroxamic acid-based HDAC inhibitor, prolongs survival in an orthotopic mouse model of pancreatic cancer. AES-135 inhibits HDAC3, HDAC6, HDAC8, and HDAC11 with IC50s ranging from 190-1100 nM.
Nature. 2021 Mar;591(7850):477-481. Cell Metab. 2021 Mar 2;33(3):565-580.e7. Nat Cell Biol. 2021 Mar;23(3):257-267. Cancer Cell. 2021 Mar 8;39(3):380-393.e8.
PROTAC linker connects a ligand to the target protein and a ligand to the E3 ubiquitin ligase. MCE possesses thousands of PROTAC linkers for PROTAC systhesis, which are three main types: PEGs-, Alkyl-Chains- and Alkyl/ether- based linkers.