JDQ-443|CAS 2653994-08-0|DC Chemicals

Cas No.:	2653994-08-0
Chemical Name:	Opnurasib
Synonyms:	2-Propen-1-one, 1-[6-[(4R)-4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methyl-1H-indazol-5-yl)-1H-pyrazol-1-yl]-2-azaspiro[3.3]hept-2-yl]-;JDQ-443;JDQ-443 (Synonyms: NVP-JDQ443);NVP-JDQ443;Opnurasib
SMILES:	CC1N(C2CC3(CN(C(=O)C=C)C3)C2)N=C(C2=CC=C3N(C)N=CC3=C2)C=1C1C(=C(C)C=C2NN=CC=12)Cl
Formula:	C₂₉H₂₈ClN₇O
M.Wt:	526.03
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
Publication:	[1]. LIU BO, et al. PYRAZOLYL DERIVATIVES USEFUL AS ANTI-CANCER AGENTS. Patent WO2021120890A1.

Description:	JDQ-443 (example 1a) is a covalent KRAS G12C inhibitor (extracted from patent WO2021120890A1)[1].
Target:	KRas G12C
In Vitro:	JDQ-443 (NVP-JDQ443) traps the GDP-bound inactive conformation of KRAS[1].
References:	[1]. LIU BO, et al. PYRAZOLYL DERIVATIVES USEFUL AS ANTI-CANCER AGENTS. Patent WO2021120890A1.

Cat. No.	Product name	Field of application
DC58063	HG106	HG106 is a potent SLC7A11 inhibitor and enhances ROS generation, ER stress, and ultimately growth arrest specifically in KRAS-mutant lung adenocarcinoma (LUAD).
DC74365	RMC-4998	RMC-4998 (RMC4998) is a tricomplex inhibitor that targets the active state or GTP-bound state of KRAS G12C, selectively inhibits the proliferation of KRASG12C mutant cells with mean IC50 of 0.28 nM.
DC74360	BC-DXI-32982	BC-DXI-32982 is a potent inhibitor of the interaction between DX2 and KRAS4B with a half-maximal inhibitory concentration (IC50) of 0.18 μM, showing little effect on the PRKACA-PRKAR2A interaction.
DC70730	Ras binder 2C07	Ras binder 2C07 is a switch-II binding ligand which binds Ras GDP and GTP states.
DC70578	LY-3537982	LY-3537982 (LY3537982) is a highly selective and potent KRAS-G12C inhibitor, selectively inhibits growth of KRAS G12C mutant cells (IC50=1-60 nM).LY-3537982 does not inhibit growth of KRAS G12S/G13C/G12D mutant cells and WT KRAS cells (CI50>10 uM).LY-3537982 displays high selectivity for proteome-wide cysteine residues was evaluated using competitive chemical proteomics (8866 peptides).LY3537982 inhibits the growth of subcutaneous EL3187 NSCLC PDX tumors in nude mice in a dose dependent manner.LY3537982 demonstrates robust tumor regression in combination with other agents in KRAS G12C in vivo models.LY3537982 is a promising KRAS G12C inhibitor predicted to deliver >90% KRAS G12C target occupancy in the clinic.
DC70535	KAL-21404358	KAL-21404358 (KAL21404358) is a small-molecule, allosteric inhibitor of K-Ras(G12D), binds to K-Ras(G12D) P110 site with KD of 88 uM in MST assay; KAL-21404358 disrupts the K-RasG12D-B-Raf interaction using a NanoBiT split luciferase assay, and to impair the Raf-MEK-ERK and the PI3K-AKT signaling pathways. KAL-21404358 exhibited specificity for K-RasG12D over K-RasWT, H-RasWT, Rap1a, R-Ras and R-Ras2.
DC70512	IODVA1	IODVA1 is a small molecule with cellular inhibitory activity against several transformed cell lines including Ras-driven cells, targets Rac activation and signaling instead of Ras; IODVA1 inhibits ST8814 cell proliferation with GI50 of 1 uM, similar results were observed with MCF7, MDA-MB-231, and T47D cells with estimated GI50s <1 uM. IODVA1 significantly decreases number of colonies of the breast cancer cells in soft agar at 1 and 3 uM. IODVA1 probably does not bind Ras and that its mechanism of action is likely Ras-independent, inhibits lamellipodia and circular dorsal ruffle (CDR) formation in MDA-MB-231 cells and decreases Rac activation. IODVA1 inhibits Rac activation and downstream signaling leading to inhibition of lamellipodia and CDR formation; IODVA1 inhibits cell-substratum and cell-cell interactions, does not target kinases, and reduces tumor burden of solid tumors in vivo.
DC70371	DW0254	DW0254 (DW-0254,DW 0254) is a small molecules capable of inhibiting RAS-related C3 botulinum toxin substrate (RAC) small GTPase activation in ALL cell lines, directly binds to the hydrophobic pocket of PDE6D (Kd=436 nM, ITC), a RAS chaperone protein.DW0254 demonstrated dose-dependent RAC inhibition, arrest of proliferation and induced apoptosis in human leukemic cell lines (RS4;11 IC50=1.5-1.8 uM), also showed promising anti-leukemic activity in RAS-mutated cells (CCRF-CEM NRAS G12D, IC50=3.3-4.2 uM).DW0254 disrupted the interaction between PDE6D and RAS, disturbing RAS subcellular localization.DW0254 demonstrated anti-leukemic activity, decreased tumor progression in a murine xenograft model.
DC70046	MRTX 0902	MRTX0902 is a potent SOS1 inhibitor with an IC50 of 46 nM (WO2021127429A1; Example 12-10).
DC47351	ASP2453	ASP2453 is a potent, selective and covalent KRAS G12C inhibitor. ASP2453 inhibits the Son of Sevenless (SOS)-mediated interaction between KRAS G12C and Raf with an IC50 value of 40 nM.