- Inhibitory Selectivity
|Catalog No.||Product Name||Solubility(25°C)|
|S1124||BMS-754807||<1 mg/mL||92 mg/mL||92 mg/mL|
|S2891||GW441756||<1 mg/mL||25 mg/mL||<1 mg/mL|
|S7519||GNF-5837||<1 mg/mL||100 mg/mL||9 mg/mL|
|S8348||BMS-935177||<1 mg/mL||100 mg/mL||100 mg/mL|
|S7998||Entrectinib (RXDX-101)||<1 mg/mL||100 mg/mL||75 mg/mL|
|S8573||Sitravatinib (MGCD516)||<1 mg/mL||100 mg/mL||100 mg/mL|
|S8407||PF-06273340||<1 mg/mL||95 mg/mL||1 mg/mL|
|S8511||Belizatinib (TSR-011)||<1 mg/mL||100 mg/mL||100 mg/mL|
|S7960||Larotrectinib (LOXO-101) sulfate||<1 mg/mL||100 mg/mL||100 mg/mL|
|S7745||ANA-12||<1 mg/mL||37 mg/mL||<1 mg/mL|
|S8319||7,8-Dihydroxyflavone||<1 mg/mL||50 mg/mL||1 mg/mL|
- Trk receptor Inhibitors (11)
- New Trk receptor Products
|Catalog No.||Information||Product Use Citations||Product Validations|
BMS-754807 is a potent and reversible inhibitor of IGF-1R/InsR with IC50 of 1.8 nM/1.7 nM in cell-free assays, less potent to Met, Aurora A/B, TrkA/B and Ron, and shows little activity to Flt3, Lck, MK2, PKA, PKC etc. Phase 2.
GW441756 is a potent, selective inhibitor of TrkA with IC50 of 2 nM, with very little activity to c-Raf1 and CDK2.
Effect of TrkA inhibitorGW441756 on vorinostat andNGFmediated ERK phosphorylation. A)NS-1 cellswere treatedwith vorinostat (1 and 2.5 μM) andNGF (2.5 ng/mL)with and without GW441756 (1 μM) for 3 h. The blots were probed with anti-pERK.1/2 antibody. Vorinostat mediated activation of ERK1/2 phosphorylation (pErk) was abolished in presence of GW441756. Total ERK levels were checked using ERK 1/2 antibody. B) Bar graph represents the densitometric analysis of immunoblots. X axis represents treatments and Y axis represents the ratio of absolute relative density of pERK to the total ERK. The data sets are the mean ± SE of two biological replicates from two independent experiments (values compared to control vs vorinostat 1 μM and 2.5 μM, vorinostat 1 μM and 2.5 μM Vs GW441756 + vorinostat 1 and 2.5 μM respectively). *P < 0.05, **P < 0.001, ***P < 0.0001 indicate significant differences and ns indicates non-significant difference.
GNF-5837 is a selective, and orally bioavailable pan-TRK inhibitor for TrkA, and TrkB with IC50 of 8 nM, and 12 nM, respectively.
BMS-935177 is a potent, reversible Bruton's Tyrosine Kinase (BTK) inhibitor with an IC50 value of 2.8 nM and demonstrates good kinase selectivity. It is more potent against BTK than other kinase, including the other Tec family kinases (TEC, BMX, ITK, and TXK) over which the compound is between 5- and 67-fold selective.
Entrectinib (RXDX-101) is an orally bioavailable pan-TrkA/B/C, ROS1 and ALK inhibitor with IC50 ranging between 0.1 and 1.7 nM. Phase 2.
(A) We transfected the EGFP/Eluc gene into KM12SM cells to establish KM12SM/Eluc cells. KM12SM/Eluc cells were inoculated into the brain of SCID mice. The mice were treated daily with or without entrectinib (15 mg/kg) for 37 days until the bioluminescence increased. Mean ± SE of total flux are shown in the lower panel. Then, the entrectinib-treated brain tumor was harvested at the point indicated by the orange triangle and cultured in vitro. The expanded tumor cells were named KM12SM-ER. (B) The sensitivity of KM12SM-ER and KM12SM cells to entrectinib was determined through cell viability assays, using a CCK-8 kit. The data (mean ± standard deviation [SD] of triplicate cultures) shown are representative of three independent experiments with similar results. (C) Tumor cells were treated with entrectinib (10 nmol/L) for 4 h or c-PARP for 48 h, and harvested lysates were assessed by western blotting. Data shown are representative of three independent experiments with similar results.
Sitravatinib (MGCD516) is a novel small molecule inhibitor targeting multiple RTKs involved in driving sarcoma cell growth, including c-Kit, PDGFRβ, PDGFRα, c-Met, and Axl.
PF-06273340 is a highly potent, kinases elective, well-tolerated pan-Trk inhibitor with IC50 values of 6, 4, 3 nM for TrkA, TrkB, Trk C, respectively.
"Belizatinib (TSR-011) is a potent inhibitor of ALK (IC50=0.7 nM) and tropomyosin receptor kinase (TRK) (IC50 values less than 3 nM for TRK A, B, and C). "
Larotrectinib (LOXO-101) sulfate is an oral potent and selective ATP-competitive inhibitor of tropomyosin receptor kinases (TRK).
Quantification of colony formation in (A), shown as a percentage of the control for NCIH2077 and RT112. Mean (3 biological replicates) +/- standard deviation (SD) shown (* p-value < 0.05, ** < 0.005, *** < 0.0005, two-sided t-test, comparing combination treatment to BGJ398 treatment). ns = not significant. (BGJ, BGJ398; Tram, Trametinib; BKM, BKM120; AZD, 8931; LDC, LDC1267; LOXO, LOXO-101; Imat, Imatinib; MGCD, MGCG-265).
ANA-12 is a selective TrkB antagonist with Kd of 10 nM and 12 μM for the high and low affinity sites, respectively.
7,8-Dihydroxyflavone acts as a potent and selective small-molecule agonist of the TrkB receptor (Kd ≈ 320 nM), the main signaling receptor of brain-derived neurotrophic factor (BDNF).