CEP-40783|cas: 1437321-24-8
DC Chemicals, Website: www.dcchemicals.com
Product Name: CEP-40783|Cas Number: 1437321-24-8| Catalog Number: DC10337|Other Nmaes: CEP 40783; CEP40783; RXDX-1063
CEP-40783 is a potent, selective and orally available inhibitor of AXL and c-Met with IC50 values of 7 nM and 12 nM, respectively.
In AXL-transfected 293GT cells, CEP-40783 is 27-fold more active compared to recombinant enzyme with an IC50 value of 0.26 nM. CEP-40783 also demonstrates superior activity against c-Met in GTL-16 cells (IC50=6 nM). The increased inhibitory activity of CEP-40783 in cells could be attributed to its extended residence time on both AXL and c-Met, consistent with a Type II mechanism. CEP-40783 shows high kinome selectivity against 298 kinases with an S90 of 0.04 (fraction of kinases showing >90% inhibition at 1 µM)[1].CEP-40783 shows dose- and time-dependent inhibition of AXL phosphorylation using NCI-H1299 NSCL xenografts with 80% target inhibition at 0.3 mg/kg 6 h post dose and complete target inhibition to >90% inhibition at 1 mg/kg between 6-24 h, while a 10 mg/kg po dose resulted in complete AXL inhibition up to 48 h post dosing[1]. In 3/5 (60%) of the tumor models, CEP-40783 shows in vivo efficacy, including tumor regressions, significantly superior to that achieved with an optimal regimen of paclitaxel. In 4/4 (100%) of the erlotinib-insensitive tumor models, CEP-40783 demonstrates significant efficacy (66 to 118% TGI) compared to the control group at the 30 mg/kg dose. Additionally, CEP-40783 in combination with erlotinib demonstrate superior anti-tumor efficacy compared to CEP-40783 and erlotinib single agents in the one erlotinib-sensitive model evaluated. CEP-40783 as a single agent and in combination with erlotinib are well tolerated[2].
2017年11月30日星期四
Coenzyme Q9|cas: 303-97-9
Coenzyme Q9|cas: 303-97-9
DC Chemicals, Website: www.dcchemicals.com
Product Name: Coenzyme Q9|Cas Number: 303-97-9| Catalog Number: DC10336|Other Nmaes: Ubiquinone Q9; CoQ9; Ubiquinone 9
Coenzyme Q9, a nine isoprenyl group-containing member of the ubiquinone family, is a normal constituent of human plasma.
Both CoQ9 and CoQ10 are equally cardioprotective, as evidenced by their abilities to improve left ventricular performance and to reduce myocardial infarct size and cardiomyocyte apoptosis. HPLC analysis reveals that a substantial portion of CoQ9 has been converted into CoQ10[1]. CoQ10 and CoQ9 are components of themitochondrial respiratory chain in mammals and can regulate some mitochondrial proteins/functions. Soybean, corn, and rapeseed oils are very rich sources of CoQ10, whereas CoQ9 has been found in high concentrations in corn oil[2].The lack of a functional CoQ9 protein in homozygous CoQ9 mutant (CoQ9(X/X)) mice causes a severe reduction in the CoQ7 protein and a widespread CoQ deficiency and accumulation of demethoxyubiquinone. The deficit in CoQ induces a brain-specific impairment of mitochondrial bioenergetics performance, a reduction in respiratory control ratio, ATP levels and ATP/ADP ratio and specific loss of respiratory complex I. These effects lead to neuronal death and demyelinization with severe vacuolization and astrogliosis in the brain of CoQ9 (X/X) mice that consequently die between 3 and 6 months of age[3].
DC Chemicals, Website: www.dcchemicals.com
Product Name: Coenzyme Q9|Cas Number: 303-97-9| Catalog Number: DC10336|Other Nmaes: Ubiquinone Q9; CoQ9; Ubiquinone 9
Coenzyme Q9, a nine isoprenyl group-containing member of the ubiquinone family, is a normal constituent of human plasma.
Both CoQ9 and CoQ10 are equally cardioprotective, as evidenced by their abilities to improve left ventricular performance and to reduce myocardial infarct size and cardiomyocyte apoptosis. HPLC analysis reveals that a substantial portion of CoQ9 has been converted into CoQ10[1]. CoQ10 and CoQ9 are components of themitochondrial respiratory chain in mammals and can regulate some mitochondrial proteins/functions. Soybean, corn, and rapeseed oils are very rich sources of CoQ10, whereas CoQ9 has been found in high concentrations in corn oil[2].The lack of a functional CoQ9 protein in homozygous CoQ9 mutant (CoQ9(X/X)) mice causes a severe reduction in the CoQ7 protein and a widespread CoQ deficiency and accumulation of demethoxyubiquinone. The deficit in CoQ induces a brain-specific impairment of mitochondrial bioenergetics performance, a reduction in respiratory control ratio, ATP levels and ATP/ADP ratio and specific loss of respiratory complex I. These effects lead to neuronal death and demyelinization with severe vacuolization and astrogliosis in the brain of CoQ9 (X/X) mice that consequently die between 3 and 6 months of age[3].
BGB-3111|cas: 1633350-06-7
BGB-3111|cas: 1633350-06-7
DC Chemicals, Website: www.dcchemicals.com
Product Name: BGB-3111|Cas Number: 1633350-06-7| Catalog Number: DC10335|Other Nmaes: BGB3111; BGB 3111
BGB-3111 is a potent, selective and orally available Bruton's tyrosine kinase (Btk) inhibitor.
In both biochemical and cellular assays, BGB-3111 demonstrates nanomolar Btk inhibition activity. In several MCL and DLBCL cell lines, BGB-3111 inhibits BCR aggregation-triggered Btk autophosphorylation, blocks downstream PLC-γ2 signaling, and potently inhibits cell proliferation. In comparison with ibrutinib, BGB-3111 shows much more restricted off-target activities against a panel of kinases, including ITK. BGB-3111 is at least 10-fold weaker than ibrutinib in inhibiting rituximab induced ADCC, consistent with its weak ITK inhibition activity[1].BGB-3111 induces dose-dependent anti-tumor effects against REC-1 MCL xenografts engrafted either subcutaneously or systemically via tail vein injection in mice. In the subcutaneous xenografts. Preliminary 14-day toxicity study in rats shows that BGB-3111 is very well tolerated and maximal tolerate dose (MTD) is not reached when it is dosed up to 250mg/kg/day[1].
DC Chemicals, Website: www.dcchemicals.com
Product Name: BGB-3111|Cas Number: 1633350-06-7| Catalog Number: DC10335|Other Nmaes: BGB3111; BGB 3111
BGB-3111 is a potent, selective and orally available Bruton's tyrosine kinase (Btk) inhibitor.
In both biochemical and cellular assays, BGB-3111 demonstrates nanomolar Btk inhibition activity. In several MCL and DLBCL cell lines, BGB-3111 inhibits BCR aggregation-triggered Btk autophosphorylation, blocks downstream PLC-γ2 signaling, and potently inhibits cell proliferation. In comparison with ibrutinib, BGB-3111 shows much more restricted off-target activities against a panel of kinases, including ITK. BGB-3111 is at least 10-fold weaker than ibrutinib in inhibiting rituximab induced ADCC, consistent with its weak ITK inhibition activity[1].BGB-3111 induces dose-dependent anti-tumor effects against REC-1 MCL xenografts engrafted either subcutaneously or systemically via tail vein injection in mice. In the subcutaneous xenografts. Preliminary 14-day toxicity study in rats shows that BGB-3111 is very well tolerated and maximal tolerate dose (MTD) is not reached when it is dosed up to 250mg/kg/day[1].
ARV-771|cas: 1949837-12-0
ARV-771|cas: 1949837-12-0
DC Chemicals, Website: www.dcchemicals.com
Product Name: ARV-771|Cas Number: 1949837-12-0| Catalog Number: DC10334|Other Nmaes: ARV 771; ARV771
ARV-771 is a potent bromodomain and extra-terminal (BET) proteins degrader with Kd values of 4.7, 7.6, 7.6 nM against bromodomain 2, 3 and 4, respectively.
ARV-771 potently degrades BRD2/3/4 in 22Rv1 cells with a DC50 less than 5 nM. c-MYC protein is a downstream effector of BET proteins. Treatment with ARV-771 results in depletion of c-MYC with an IC50 of less than 1 nM. ARV-771 shows strong antiproliferative effect on 22Rv1, VCaP, and LnCaP95 cell lines. ARV-771 treatment has a pronounced effect on cell morphology consistent with apoptosis. FL-AR and AR-V7 mRNA are down-regulated upon treatment with 10 nM ARV-771 in VCaP cells. ARV-771 has an antiandrogenic effect on a number of AR-regulated genes in VCaP cells[1].Treatment of non castrated male Nu/Nu mice bearing AR-V7+ 22Rv1 tumor xenografts with daily subcutaneous injections of ARV-771 at 10 mg/kg for 3 d results in 37% and 76% down-regulation of BRD4 and c-MYC levels, respectively, in tumor tissue. A marked down-regulation in levels of AR-V7 is observed in the 22Rv1 tumors after ARV-771 treatment[1].
DC Chemicals, Website: www.dcchemicals.com
Product Name: ARV-771|Cas Number: 1949837-12-0| Catalog Number: DC10334|Other Nmaes: ARV 771; ARV771
ARV-771 is a potent bromodomain and extra-terminal (BET) proteins degrader with Kd values of 4.7, 7.6, 7.6 nM against bromodomain 2, 3 and 4, respectively.
ARV-771 potently degrades BRD2/3/4 in 22Rv1 cells with a DC50 less than 5 nM. c-MYC protein is a downstream effector of BET proteins. Treatment with ARV-771 results in depletion of c-MYC with an IC50 of less than 1 nM. ARV-771 shows strong antiproliferative effect on 22Rv1, VCaP, and LnCaP95 cell lines. ARV-771 treatment has a pronounced effect on cell morphology consistent with apoptosis. FL-AR and AR-V7 mRNA are down-regulated upon treatment with 10 nM ARV-771 in VCaP cells. ARV-771 has an antiandrogenic effect on a number of AR-regulated genes in VCaP cells[1].Treatment of non castrated male Nu/Nu mice bearing AR-V7+ 22Rv1 tumor xenografts with daily subcutaneous injections of ARV-771 at 10 mg/kg for 3 d results in 37% and 76% down-regulation of BRD4 and c-MYC levels, respectively, in tumor tissue. A marked down-regulation in levels of AR-V7 is observed in the 22Rv1 tumors after ARV-771 treatment[1].
PTP1B-IN-2｜PTP1B inhibitor｜cas 1919853-46-5
PTP1B-IN-2｜PTP1B inhibitor｜cas 1919853-46-5
DC Chemicals, Website: www.dcchemicals.com
Product Name: PTP1B-IN-2|Cas Number: 1919853-46-5| Catalog Number: DC10333|Other Nmaes: PTP1B-IN-2,PTP1B inhibitor 2
PTP1B-IN-2 is a novel protein tyrosine phosphatase-1B (PTP1B) inhibitor
DC Chemicals, Website: www.dcchemicals.com
Product Name: PTP1B-IN-2|Cas Number: 1919853-46-5| Catalog Number: DC10333|Other Nmaes: PTP1B-IN-2,PTP1B inhibitor 2
PTP1B-IN-2 is a novel protein tyrosine phosphatase-1B (PTP1B) inhibitor
MT-DADMe-ImmA|cas 653592-04-2
MT-DADMe-ImmA|cas 653592-04-2
DC Chemicals, Website: www.dcchemicals.com
Product Name: MT-DADMe-ImmA|Cas Number: 653592-04-2| Catalog Number: DC10332|Other Nmaes: Methylthio-DADMe-Immucillin A; MTDIA
MT-DADMe-ImmA is an inhibitor of human 5'-methylthioadenosine phosphorylase (MTAP) with a Ki of 90 pM.
Treatment of cultured cells with MT-DADMe-ImmA and MTA inhibit MTAP, increase cellular MTA concentrations, decrease polyamines, and induce apoptosis in FaDu and Cal27, two head and neck squamous cell carcinoma cell lines. The same treatment does not induce apoptosis in normal human fibroblast cell lines (CRL2522 and GM02037) or in MCF7, a breast cancer cell line with an MTAP gene deletion. MT-DADMe-ImmA alone does not induce apoptosis in any cell line, implicating MTA as the active agent[2].The t1/2 for onset of inhibition is 50 min with complete inhibition by 250 min. MTAP activity slowly returns, giving a biological half-life for the action of oral MT-DADMe-ImmA of 6.3 days. The time-dependent growth of FaDu tumors in immunodeficient mice is suppressed by oral or intraperitoneal treatment with MT-DADMe-ImmA[2].
DC Chemicals, Website: www.dcchemicals.com
Product Name: MT-DADMe-ImmA|Cas Number: 653592-04-2| Catalog Number: DC10332|Other Nmaes: Methylthio-DADMe-Immucillin A; MTDIA
MT-DADMe-ImmA is an inhibitor of human 5'-methylthioadenosine phosphorylase (MTAP) with a Ki of 90 pM.
Treatment of cultured cells with MT-DADMe-ImmA and MTA inhibit MTAP, increase cellular MTA concentrations, decrease polyamines, and induce apoptosis in FaDu and Cal27, two head and neck squamous cell carcinoma cell lines. The same treatment does not induce apoptosis in normal human fibroblast cell lines (CRL2522 and GM02037) or in MCF7, a breast cancer cell line with an MTAP gene deletion. MT-DADMe-ImmA alone does not induce apoptosis in any cell line, implicating MTA as the active agent[2].The t1/2 for onset of inhibition is 50 min with complete inhibition by 250 min. MTAP activity slowly returns, giving a biological half-life for the action of oral MT-DADMe-ImmA of 6.3 days. The time-dependent growth of FaDu tumors in immunodeficient mice is suppressed by oral or intraperitoneal treatment with MT-DADMe-ImmA[2].
Tebanicline hydrochloride|cas 203564-54-9
Tebanicline hydrochloride|cas 203564-54-9
DC Chemicals, Website: www.dcchemicals.com
Product Name: Tebanicline hydrochloride|Cas Number: 203564-54-9| Catalog Number: DC10331|Other Nmaes: Ebanicline hydrochloride; ABT594 hydrochloride; ABT-594 hydrochloride; ABT 594 hydrochloride
Tebanicline hydrochloride (ABT594 hydrochloride) is a nAChR modulator with potent, orally effective analgesic activity. It inhibits the binding of cytisine to α4β2 neuronal nAChRs with a Ki of 37 pM.
Tebanicline is a novel, potent cholinergic nAChR ligand with analgesic properties that shows preferential selectivity for neuronal nAChRs. It inhibits the binding of cytisine to α4β2 neuronal nAChRs with a Ki of 37 pM. Functionally, tebanicline is an agonist. At the transfected human α4β2 neuronal nAChR in K177 cells, with increased 86Rb+ efflux as a measure of cation efflux, ABT-594 has an EC50 value of 140 nM with an intrinsic activitycompared with (−)-nicotine of 130%; at the nAChR subtype expressed in IMR-32 cells, an EC50 of 340 nM; at the F11 dorsal root ganglion cell line, an EC50 of 1220 nM; and via direct measurement of ion currents, an EC50 value of 56,000 nM at the human α7 homo-oligimeric nAChR produced in oocytes[1]Tebanicline is a potent antinociceptive agent with full efficacy in models of acute and persistent pain and that these effects are mediated predominately by an action at central neuronal nAChRs[2]. Tebanicline produces significant antinociceptive effects in mice against both acute noxious thermal stimulation. ABT-594 is orally active, but 10-fold less potent by this route than after i.p. administration. The antinociceptive effect of ABT-594 is prevented, but not reversed, by the noncompetitive neuronal nicotinic acetylcholine receptor antagonist[3]. Tebanicline has antinociceptive effects in rat models of acute thermal, persistent chemical, and neuropathic pain. Direct injection of tebanicline into the nucleus raphe magnus (NRM) is antinociceptive in a thermal threshold test and destruction of serotonergic neurons in the NRM attenuates the effect of systemic tebanicline[4].
DC Chemicals, Website: www.dcchemicals.com
Product Name: Tebanicline hydrochloride|Cas Number: 203564-54-9| Catalog Number: DC10331|Other Nmaes: Ebanicline hydrochloride; ABT594 hydrochloride; ABT-594 hydrochloride; ABT 594 hydrochloride
Tebanicline hydrochloride (ABT594 hydrochloride) is a nAChR modulator with potent, orally effective analgesic activity. It inhibits the binding of cytisine to α4β2 neuronal nAChRs with a Ki of 37 pM.
Tebanicline is a novel, potent cholinergic nAChR ligand with analgesic properties that shows preferential selectivity for neuronal nAChRs. It inhibits the binding of cytisine to α4β2 neuronal nAChRs with a Ki of 37 pM. Functionally, tebanicline is an agonist. At the transfected human α4β2 neuronal nAChR in K177 cells, with increased 86Rb+ efflux as a measure of cation efflux, ABT-594 has an EC50 value of 140 nM with an intrinsic activitycompared with (−)-nicotine of 130%; at the nAChR subtype expressed in IMR-32 cells, an EC50 of 340 nM; at the F11 dorsal root ganglion cell line, an EC50 of 1220 nM; and via direct measurement of ion currents, an EC50 value of 56,000 nM at the human α7 homo-oligimeric nAChR produced in oocytes[1]Tebanicline is a potent antinociceptive agent with full efficacy in models of acute and persistent pain and that these effects are mediated predominately by an action at central neuronal nAChRs[2]. Tebanicline produces significant antinociceptive effects in mice against both acute noxious thermal stimulation. ABT-594 is orally active, but 10-fold less potent by this route than after i.p. administration. The antinociceptive effect of ABT-594 is prevented, but not reversed, by the noncompetitive neuronal nicotinic acetylcholine receptor antagonist[3]. Tebanicline has antinociceptive effects in rat models of acute thermal, persistent chemical, and neuropathic pain. Direct injection of tebanicline into the nucleus raphe magnus (NRM) is antinociceptive in a thermal threshold test and destruction of serotonergic neurons in the NRM attenuates the effect of systemic tebanicline[4].
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