CCG-100602|CAS 1207113-88-9|DC Chemicals

Cas No.:	1207113-88-9
Chemical Name:	[3,5-Bis(trifluoromethyl)benzoyl]-N-(4-chlorophenyl)piperidine-3-carboxamide
Synonyms:	Ccg-100602;[3,5-bis(trifluoromethyl)benzoyl]-N-(4-chlorophenyl)piperidine-3-carboxamide
SMILES:	ClC1C=CC(=CC=1)N(C(C1C=C(C(F)(F)F)C=C(C(F)(F)F)C=1)=O)C(C1CNCCC1)=O
Formula:	C₂₁H₁₇ClF₆N₂O₂
M.Wt:	478.81530547142
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	CCG-100602 is a specific inhibitor of myocardin-related transcription factor A/serum response factor (MRTF-A/SRF) signaling. CCG-100602 specifically block MRTF-A nuclear localization and thus inhibit the fibrogenic transcription factor SRF.
In Vivo:	Treatment with CCG-100602 (7.5 mg/kg/day, continuously administered for 2 weeks by osmotic minipumps) abrogates the increase of aortic stiffness represented by reduced arterial compliance and strain, indicating a significant anti-stiffening effect resulting from the inhibition of SRF/myocardin[3]. Animal Model: Adult (4 month-old) male spontaneously hypertensive rats (SHR) and normotensive control Wistar-Kyoto (WKY) rats[3] Dosage: 7.5 mg/kg/day Administration: Continuously administered for 2 weeks by osmotic minipumps. Result: Abrogated the increase of aortic stiffness represented by reduced arterial compliance and strain.
In Vitro:	CCG-100602 (3-30 μM) decreases the number of adherent hASC cells[2]. CCG-100602 blocks the expression of MRTF-A/SRF-activated genes[2]. CCG-100602 (5-40 μM) diminishes the TGF-β1 (5 ng/mL)-induced increase in COL1A1, FN1, and ACTA2 transcription in a dose-dependent manner[1]. CCG-100602 (5-40 μM) reduces the TGF-β1-induced increase in MRTFA and SRF mRNA expression in the HIMFs in a dose-dependent manner [1]. CCG-100602 (5-40 μM) significantly reduces the protein expression levels of the ECM and α-SMA in TGF-β1 (5 ng/mL)-stimulated cells in a dose-dependent manner[1]. CCG-100602 (5-40 μM) also significantly represses the MRTF-A and SRF protein expression, which were induced by TGF-β1, in the nuclear fraction of the HIMFs in a dose-responsive manner[1]. Cell Viability Assay[2] Cell Line: Human adipose stem cell (hASC) Concentration: 3, 8, 15, or 30 μM Incubation Time: 7 days Result: The number of adherent cells decreased as a response to increasing inhibitor amount. The effect was also dependent on the culture media because the osteogenic medium condition supported the viability over basic culture medium and adipogenic medium conditions. RT-PCR[1] Cell Line: Human intestinal myofibroblasts (HIMFs) Concentration: 5, 10, 20, and 40 μM Incubation Time: 30 min prior to the addition of TGF-β1 (5 ng/mL) for 24 hours Result: Diminished the TGF-β1-induced increase in COL1A1, FN1, and ACTA2 transcription in a dose-dependent manner. Reduced the TGF-β1-induced increase in MRTFA and SRF mRNA expression in the HIMFs in a dose-dependent manner. Western Blot Analysis[1] Cell Line: Human intestinal myofibroblasts (HIMFs) Concentration: 5, 10, 20, and 40 μM Incubation Time: 30 min prior to the addition of TGF-β1 (5 ng/mL) for 48 hours Result: The protein expression levels of the ECM and α-SMA in TGF-β1-stimulated cells are significantly reduced. Repressed the MRTF-A and serum response factor (SRF) protein expression, which were induced by TGF-β1, in the nuclear fraction of the HIMFs.
References:	[1]. Yoon Jeong Choi, et al. Umbilical cord/placenta-derived mesenchymal stem cells inhibit fibrogenic activation in human intestinal myofibroblasts via inhibition of myocardin-related transcription factor A. Stem Cell Res Ther. 2019 Sep 23;10(1):291. [2]. Laura Hyväri, et al. Myocardin-Related Transcription Factor A (MRTF-A) Regulates the Balance between Adipogenesis and Osteogenesis of Human Adipose Stem Cells. Stem Cells Int. 2020 Sep 22;2020:8853541. [3]. Ning Zhou, et al. Rho Kinase Regulates Aortic Vascular Smooth Muscle Cell Stiffness Via Actin/SRF/Myocardin in Hypertension. Cell Physiol Biochem. 2017;44(2):701-715.

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).
DC78346	AH001	AH001 is a orally active RhoA inhibitor, which binds a cryptic pocket proximate to GDP within RhoA with a KD of 73.16 nM. AH001 interacts with GDP, stabilizing RhoA’s interaction with its endogenous inhibitor, RhoGDIα. AH001 reduces the downstream MRTFA nuclear translocation and downregulates fibrosis/hypertrophy proteins. AH001 mitigates myocardial remodeling in multiple HF animal models, and in the 3D myocardial tissue model. AH001 exerts its cardioprotective effects through the RhoA-RhoGDIα axis, effectively inhibiting downstream RhoA activation signaling.
DC77133	AMG410	AMG410 is a non-covalent and selective pan-KRAS inhibitor with IC50 values of 1-4 nM for KRAS G12D, KRAS G12V, and KRAS G13D. AMG410 shows greater than 100-fold selectivity against both HRAS and NRAS. AMG410 is a dual GTP(on)- and GDP(off)-state inhibitor (Kd(GDP-state) of 1 nM; Kd(GTP-state) of 22 nM). AMG410 blocks KRAS signaling in a cycling state-independent manner and also blocks proliferation in wildtype KRAS-amplified tumor cells. AMG410 can be used for the study of colorectal, pancreatic, and lung cancers.
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.
DC74356	ACA22	ACA22 is a small molecule KRAS inhibitor, inhibits KRAS-mediated signal transduction in cells expressing wild type (WT) and G12D mutant KRAS.
DC74355	ACA-14	ACA-14 is a small molecule direct inhibitor of KRAS, impedes the interaction of KRAS with its effector Raf and reduces both intrinsic and SOS-mediated nucleotide exchange rates.
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.