*New Arrival Archives - TheKaneShop

PF-06700841

andreas — Tue, 28 Apr 2020 08:23:35 +0000

PF-06700841 is a potent inhibitor of Tyk2 and Jak1 with IC50s of 23 nM, 17 nM, 77 nM for Tyk2, Jak1 and Jak2 respectively. It has appropriate in-family selectivity against JAK2 and JAK3.

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Tofacitinib (CP-690550）

andreas — Tue, 28 Apr 2020 08:13:02 +0000

Tofacitinib (CP-690550,Tasocitinib) is a novel inhibitor of JAK3 with IC50 of 1 nM in cell-free assays, 20- to 100-fold less potent against JAK2 and JAK1.

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Ruxolitinib

andreas — Tue, 28 Apr 2020 08:05:41 +0000

Ruxolitinib (INCB018424) is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM in cell-free assays, >130-fold selectivity for JAK1/2 versus JAK3.

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PF-06651600

andreas — Tue, 28 Apr 2020 07:58:53 +0000

PF-06651600 is a potent and irreversible JAK3-selective inhibitor with an IC50 of 33.1 nM but without activity (IC50 > 10 000 nM) against JAK1, JAK2, and TYK2.

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Baricitinib (LY3009104)

andreas — Tue, 28 Apr 2020 07:49:18 +0000

Baricitinib (LY3009104, INCB028050) is a selective JAK1 and JAK2 inhibitor with IC50 of 5.9 nM and 5.7 nM in cell-free assays, ~70 and ~10-fold selective versus JAK3 and Tyk2, no inhibition to c-Met and Chk2. Phase 3.

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SM04554

andreas — Thu, 19 Mar 2020 02:21:40 +0000

SM04554 is a topical compound that modulates the WNT pathway. The WNT pathway is one of the primary signalling pathways that regulate the self-renewal and differentiation of adult stem cells. It also plays other important roles: from hair follicle cycling to hair follicle morphogenesis.

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Nocodazole

andreas — Mon, 29 Apr 2019 03:16:34 +0000

Nocodazole is an anti‐mitotic drug that has long been used as an experimental tool in cell biology. Although nocodazole is known to bind with high affinity to tubulin and to inhibit microtubule assembly, very little has been done on its precise mechanism of action. In fact, its binding to the different isotypes of tubulin has never been addressed. Although the nocodazole binding site overlaps with that of colchicine, the two drugs are structurally quite different. The tubulin molecule is an α/β heterodimer; both α and β exist as various isotypes whose distribution and drug‐binding properties are significantly different. In this study, we measured the binding affinity of nocodazole for purified tubulin isotypes. Using fluorescence quenching analysis, we found that the binding kinetics of nocodazole with each type of tubulin best fits a two‐affinity Michaelis‐Menten binding model. The apparent dissociation constants for the high‐affinity binding sites are 0.52 ± 0.02 for αβ_II, 1.54 ± 0.29 for αβ_III, and 0.29 ± 0.04 for αβ_IV. Thus, nocodazole has the highest affinity for αβ_IV and the lowest affinity for αβ_III. Knowledge of the isotype specificity of nocodazole may allow for development of novel therapeutic agents based on this drug.

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UK-5099

andreas — Mon, 29 Apr 2019 02:55:52 +0000

UK-5099 is a potent inhibitor of the mitochondrial pyruvate carrier (MPC). UK-5099 ihibits pyruvate-dependent O₂ consumption with an IC₅₀ of 50 nM.IC50 & Target: IC50: 50 nM (MPC)^[1]In Vitro: The trypanosomal pyruvate carrier is found to be rather insensitive to inhibition by alpha-cyano-4-hydroxycinnamate (K_i=17 mM) but can be completely blocked by UK-5099 (K_i=49 microM)^[2]. UK-5099 also inhibits the monocarboxylate transporter (MCT) ^[3]. UK5099 significantly inhibits the glucose-stimulated rise in oxygen consumption in a dose-dependent manner and at 150 μM reduced oxygen consumption below basal levels. UK5099 reduces ATP levels and increases ADP and AMP levels in 832/13 cells^[4]. The UK5099 treated cells show significantly higher proportion of side population fraction and express higher levels of stemness markers Oct3/4 and Nanog. UK5099 application may be an ideal

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WAY 316606 HCl

andreas — Wed, 06 Jun 2018 09:16:01 +0000

Description	WAY 316606 is an inhibitor of the secreted protein sFRP-1, an endogenous antagonist of the secreted glycoprotein Wnt. The affinity of WAY-316606 for sFRP-1 is determined using the FP binding assay with IC₅₀ of 0.5 μM.
IC₅₀ & Target	IC50: 0.5 μM (sFRP-1)^[1]
In Vitro	The EC₅₀ of WAY-316606 for Wnt-Luciferase Activity from U2-OS Cells is 0.65 μM^[1]. WAY-316606 binds to secreted frizzled-related protein (sFRP)-1 inhibitor with a K_D of 0.08 μM and inhibits sFRP-1 with an EC₅₀ of 0.65 μM. WAY-316606 also binds to sFRP-2, albeit over 10 times weaker with a K_D of 1 μM. Using a fluorescence polarization binding assay that employs a fluorescent probe compound and purified human sFRP-1 protein in a competitive-binding format, the IC₅₀ for WAY-316606 is 0.5 μM^[2].
In Vivo	WAY-316606 increases bone formation when tested in a neonatal murine calvarial assay. WAY-316606 increases total bone area up to 60% in a dose-dependent manner with an EC50 of about 1 nM. WAY-316606 has good aqueous solubility, moderate to low inhibition of cytochrome p450 isozymes (3A4, 2D6, 2C9) and good stability in rat and human liver microsomes (t_1/2>60 min in each species). In female Sprague-Dawley rats, WAY-316606 exhibits high plasma clearance (77 mL/min/kg, greater than hepatic blood flow) following a single intravenous bolus dose (2 mg/kg), which results in a rapid decline of drug exposure in the plasma despite the route of administration^[2].

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WAY-262611, HCl

andreas — Wed, 06 Jun 2018 09:03:04 +0000

Inhibitor of Dickkopf-1 (DKK1); WAY 262611 is a wingless Wnt/β-Catenin signaling agonist with an inhibitory effect on DKK1, displaying an EC50 value of 0.63 uM for DKK1-mediated TCF-Luciferase, no affinity for GSK-3β (IC50 value >100 uM) and enhancing the bone formation rate in ovariectomized (OVX) rats following oral adminstration. Dickkopf-1 (DKK1) is a soluble inhibitor of Wnt-3a mediated Wnt/β-catenin signaling required for embryonic head development. It regulates Wnt signaling by binding to the Wnt coreceptor lipoprotein-related protein-5 (LRP5)/Arrow, and Kremen2 (Kr2) simultaneously.

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