Trk receptor
Signaling Pathway Map
Research Area
Inhibitory Selectivity
Isoform-specific Inhibitors
Trk receptor Products
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S1460 |
SP600125SP600125 (Nsc75890) is a broad-spectrum JNK inhibitor for JNK1, JNK2 and JNK3 with IC50 of 40 nM, 40 nM and 90 nM in cell-free assays, respectively; 10-fold greater selectivity against MKK4, 25-fold greater selectivity against MKK3, MKK6, PKB, and PKCα, and 100-fold selectivity against ERK2, p38, Chk1, EGFR etc. SP600125 is also a broad‐spectrum inhibitor of serine/threonine kinases including Aurora kinase A，FLT3 and TRKA with of IC50 of 60 nM, 90 nM and 70 nM. SP600125 inhibits autophagy and activates apoptosis. |
Loss of DUSP4 function upregulates IL-6 and IL-8 and enhances mammosphere growth. Immunoblot analysis of MDA-231 cells after treatment of 24 hours with 1 umol/L selumetinib (MEKi) or 10 umol/L SP600125 (JNKi). I, MDA-231 mammosphere formation quantitated by GelCount software 7 days after siRNA transfection. Where indicated, selumetinib (MEKi) or SP600125 (JNK1) or the combination was added to the mammosphere cultures.
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| S1107 |
Danusertib (PHA-739358)Danusertib (PHA-739358) is an Aurora kinase inhibitor for Aurora A/B/C with IC50 of 13 nM/79 nM/61 nM in cell-free assays, modestly potent to Abl, TrkA, c-RET and FGFR1, and less potent to Lck, VEGFR2/3, c-Kit, CDK2, etc. Danusertib induces apoptosis, cell cycle arrest, and autophagy. Phase 2. |
Mice bearing subcutaneous allografts of conditional patched mutant tumor cells were treated twice weekly with vehicle (saline) or 30 mg/kg PHA-739358. (B)Images of tumors. (C) Tumor weights. Each point represents a single tumor, and grey lines represent mean tumor weights, which were significantly different between vehicle and PHA-739358 treated mice (p < 0.05, based on paired two-tailed t-test).
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| S1124 |
BMS-754807BMS-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. |
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| S2891 |
GW441756GW441756 is a potent, selective inhibitor of TrkA with IC50 of 2 nM, with very little activity to c-Raf1 and CDK2. GW441756 produces a relevant increase of caspase-3 that leads to apoptosis. |
Thermal latency and mechanical allodynia were normalized in the RTXw1 + 4MC group (n= 6). In these mice, thermal hypoalgesia reappeared within 2 days of GW441756 injection (D). GW441756 did not affect mechanical thresholds (E) in the RTXw1 + 4MC group. (F, G) The diagrams show behavioral responses of naïve mice to either gambogic amide (open square, n = 6) or GW441756 (open circle, n =6). Gambogic amide induced mild thermal hyperalgesia within 2 days of injection but GW441756 did not affect thermal latencies (F). Both gambogic amide and GW441756 did not affect mechanical responses. *P < 0.05, **P < 0.01, and ***P < 0.001: paired t-test comparing preinjection vs. postinjection effects. #P < 0.05, ##P < 0.01, and ###P < 0.001: between drugs and saline treatments.
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| S9662New |
UNC2025UNC2025 is a potent and orally active dual inhibitor of FLT3 and MER with IC50 of 0.35 nM and 0.46 nM, respectively. UNC2025 also inhibits AXL, TRKA, TRKC, QIK, TYRO3, SLK, NuaK1, KIT and Met with IC50 of 1.65 nM, 1.67 nM, 4.38 nM, 5.75 nM, 5.83 nM, 6.14 nM, 7.97 nM, 8.18 nM and 364 nM, respectively. |
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| S4903New |
K252aK252a is a non-selective protein kinase inhibitor. |
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| S8901New |
DS-6051bDS-6051b is a new-generation selective ROS1/NTRK inhibitor with ic50 of 0.207 nM,0.622 nM,2.28 nM and 0.980 nM for ROS1,NTRK1,NTRK2 and NTRK3,respectively. |
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| S7519 |
GNF-5837GNF-5837 is a selective, and orally bioavailable pan-TRK inhibitor for TrkA, and TrkB with IC50 of 8 nM, and 12 nM, respectively. |
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| S8788 |
CH7057288CH7057288 is a potent and selective TRK inhibitor with IC50 values of 1.1 nM, 7.8 nM and 5.1 nM for TRKA, TRKB, and TRKC respectively. |
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| S8348 |
BMS-935177BMS-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. |
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| S7998 |
Entrectinib (RXDX-101)Entrectinib (RXDX-101, NMS-E628) is an orally bioavailable pan-TrkA/B/C, ROS1 and ALK inhibitor with IC50 ranging between 0.1 and 1.7 nM. Entrectinib (RXDX-101) induces autophagy. Phase 2. |
Tumor cells were treated with entrectinib (10 nmol/L) for 4 hours or c-PARP for 48 hours, and harvested lysates were assessed by Western blotting. Data shown are representative of three independent experiments with similar results.
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| S8573 |
Sitravatinib (MGCD516)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. |
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| S8583 |
Repotrectinib (TPX-0005)Repotrectinib (TPX-0005) is a novel ALK/ROS1/TRK inhibitor with the IC50 values of 1.01 nM for WT ALK, 1.26 nM for ALK(G1202R), and 1.08 nM for ALK(L1196M); also a potent SRC inhibitor (IC50 5.3 nM). |
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| S8407 |
PF-06273340PF-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. |
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| S8511 |
Belizatinib (TSR-011)"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). " |
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| S8636 |
Selitrectinib (LOXO-195)Selitrectinib (LOXO-195) is an orally available, highly potent, and selective TRK kinase inhibitor with low nanomolar inhibitory activity against TRKA G595R, TRKC G623R, and TRKA G667C, IC50s ranging from 2.0 to 9.8 nmol/L. It is more than 1,000-fold selective for 98% of non-TRK kinases tested. |
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| S6412 |
AltiratinibAltiratinib is a potent single-digit nanomolar inhibitor of TRK, MET, TIE2, and VEGFR2 kinases with IC50 vaules of 0.9 nM, 4.6 nM, and 0.8 nM for TRKA, B, and C, respectively. It inhibits MET and MET mutant with IC50 values in the range of 0.3-6 nM. |
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| S7960 |
Larotrectinib (LOXO-101) sulfateLarotrectinib (LOXO-101) sulfate is an oral potent and selective ATP-competitive inhibitor of tropomyosin receptor kinases (TRK). Larotrectinib inhibition of TRKs induces cellular apoptosis and G1 cell-cycle arrest. |
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).
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| S6760New |
LM22B-10LM22B-10 is a small molecule TrkB/TrkC neurotrophin receptor co-activator, LM22B-10 selectively activates TrkB, TrkC, AKT and ERK in vivo and in vitro. |
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| S7745 |
ANA-12ANA-12 is a selective TrkB antagonist with Kd of 10 nM and 12 μM for the high and low affinity sites, respectively. |
Maternal exercise ameliorated sevoflurane-induced neuronal cell loss and decreased dendritic spine density, blocked by TrkB inhibition. Nissl staining and Golgi staining were performed after behavior tests (n = 3). (A) Nissl staining in the CA1 region of hippocampus under ×400. (B) Neuronal density ratio changes. (C) Golgi staining in the CA1 of hippocampus under ×1000. (D) Histograms represented the number of dendritic spines/10 μm. Values are mean ± S.E.M. *p < 0.05, compared with Ctrl group; **p < 0.01, compared with Ctrl group; ##p < 0.01, compared with Sevo group; ∧∧p < 0.01, compared with Sevo + ME group. One-way analysis of variance followed by Tukey post hoc multiple comparison tests was used for data analysis.
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| S0827New |
LM 22A4LM22A-4 is a specific agonist of tyrosine kinase receptor B (TrkB) with IC50 of 47 nM. LM22A-4 is used for neurological disease research. |
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| S8319 |
7,8-Dihydroxyflavone7,8-Dihydroxyflavone (7,8-DHF) 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). |
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S1460 |
SP600125SP600125 (Nsc75890) is a broad-spectrum JNK inhibitor for JNK1, JNK2 and JNK3 with IC50 of 40 nM, 40 nM and 90 nM in cell-free assays, respectively; 10-fold greater selectivity against MKK4, 25-fold greater selectivity against MKK3, MKK6, PKB, and PKCα, and 100-fold selectivity against ERK2, p38, Chk1, EGFR etc. SP600125 is also a broad‐spectrum inhibitor of serine/threonine kinases including Aurora kinase A，FLT3 and TRKA with of IC50 of 60 nM, 90 nM and 70 nM. SP600125 inhibits autophagy and activates apoptosis. |
Loss of DUSP4 function upregulates IL-6 and IL-8 and enhances mammosphere growth. Immunoblot analysis of MDA-231 cells after treatment of 24 hours with 1 umol/L selumetinib (MEKi) or 10 umol/L SP600125 (JNKi). I, MDA-231 mammosphere formation quantitated by GelCount software 7 days after siRNA transfection. Where indicated, selumetinib (MEKi) or SP600125 (JNK1) or the combination was added to the mammosphere cultures.
|
|
| S1107 |
Danusertib (PHA-739358)Danusertib (PHA-739358) is an Aurora kinase inhibitor for Aurora A/B/C with IC50 of 13 nM/79 nM/61 nM in cell-free assays, modestly potent to Abl, TrkA, c-RET and FGFR1, and less potent to Lck, VEGFR2/3, c-Kit, CDK2, etc. Danusertib induces apoptosis, cell cycle arrest, and autophagy. Phase 2. |
Mice bearing subcutaneous allografts of conditional patched mutant tumor cells were treated twice weekly with vehicle (saline) or 30 mg/kg PHA-739358. (B)Images of tumors. (C) Tumor weights. Each point represents a single tumor, and grey lines represent mean tumor weights, which were significantly different between vehicle and PHA-739358 treated mice (p < 0.05, based on paired two-tailed t-test).
|
|
| S1124 |
BMS-754807BMS-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. |
|
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| S2891 |
GW441756GW441756 is a potent, selective inhibitor of TrkA with IC50 of 2 nM, with very little activity to c-Raf1 and CDK2. GW441756 produces a relevant increase of caspase-3 that leads to apoptosis. |
Thermal latency and mechanical allodynia were normalized in the RTXw1 + 4MC group (n= 6). In these mice, thermal hypoalgesia reappeared within 2 days of GW441756 injection (D). GW441756 did not affect mechanical thresholds (E) in the RTXw1 + 4MC group. (F, G) The diagrams show behavioral responses of naïve mice to either gambogic amide (open square, n = 6) or GW441756 (open circle, n =6). Gambogic amide induced mild thermal hyperalgesia within 2 days of injection but GW441756 did not affect thermal latencies (F). Both gambogic amide and GW441756 did not affect mechanical responses. *P < 0.05, **P < 0.01, and ***P < 0.001: paired t-test comparing preinjection vs. postinjection effects. #P < 0.05, ##P < 0.01, and ###P < 0.001: between drugs and saline treatments.
|
|
| S9662New |
UNC2025UNC2025 is a potent and orally active dual inhibitor of FLT3 and MER with IC50 of 0.35 nM and 0.46 nM, respectively. UNC2025 also inhibits AXL, TRKA, TRKC, QIK, TYRO3, SLK, NuaK1, KIT and Met with IC50 of 1.65 nM, 1.67 nM, 4.38 nM, 5.75 nM, 5.83 nM, 6.14 nM, 7.97 nM, 8.18 nM and 364 nM, respectively. |
||
| S4903New |
K252aK252a is a non-selective protein kinase inhibitor. |
||
| S8901New |
DS-6051bDS-6051b is a new-generation selective ROS1/NTRK inhibitor with ic50 of 0.207 nM,0.622 nM,2.28 nM and 0.980 nM for ROS1,NTRK1,NTRK2 and NTRK3,respectively. |
||
| S7519 |
GNF-5837GNF-5837 is a selective, and orally bioavailable pan-TRK inhibitor for TrkA, and TrkB with IC50 of 8 nM, and 12 nM, respectively. |
||
| S8788 |
CH7057288CH7057288 is a potent and selective TRK inhibitor with IC50 values of 1.1 nM, 7.8 nM and 5.1 nM for TRKA, TRKB, and TRKC respectively. |
||
| S8348 |
BMS-935177BMS-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. |
||
| S7998 |
Entrectinib (RXDX-101)Entrectinib (RXDX-101, NMS-E628) is an orally bioavailable pan-TrkA/B/C, ROS1 and ALK inhibitor with IC50 ranging between 0.1 and 1.7 nM. Entrectinib (RXDX-101) induces autophagy. Phase 2. |
Tumor cells were treated with entrectinib (10 nmol/L) for 4 hours or c-PARP for 48 hours, and harvested lysates were assessed by Western blotting. Data shown are representative of three independent experiments with similar results.
|
|
| S8573 |
Sitravatinib (MGCD516)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. |
||
| S8583 |
Repotrectinib (TPX-0005)Repotrectinib (TPX-0005) is a novel ALK/ROS1/TRK inhibitor with the IC50 values of 1.01 nM for WT ALK, 1.26 nM for ALK(G1202R), and 1.08 nM for ALK(L1196M); also a potent SRC inhibitor (IC50 5.3 nM). |
||
| S8407 |
PF-06273340PF-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. |
||
| S8511 |
Belizatinib (TSR-011)"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). " |
||
| S8636 |
Selitrectinib (LOXO-195)Selitrectinib (LOXO-195) is an orally available, highly potent, and selective TRK kinase inhibitor with low nanomolar inhibitory activity against TRKA G595R, TRKC G623R, and TRKA G667C, IC50s ranging from 2.0 to 9.8 nmol/L. It is more than 1,000-fold selective for 98% of non-TRK kinases tested. |
||
| S6412 |
AltiratinibAltiratinib is a potent single-digit nanomolar inhibitor of TRK, MET, TIE2, and VEGFR2 kinases with IC50 vaules of 0.9 nM, 4.6 nM, and 0.8 nM for TRKA, B, and C, respectively. It inhibits MET and MET mutant with IC50 values in the range of 0.3-6 nM. |
||
| S7960 |
Larotrectinib (LOXO-101) sulfateLarotrectinib (LOXO-101) sulfate is an oral potent and selective ATP-competitive inhibitor of tropomyosin receptor kinases (TRK). Larotrectinib inhibition of TRKs induces cellular apoptosis and G1 cell-cycle arrest. |
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).
|
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S6760New |
LM22B-10LM22B-10 is a small molecule TrkB/TrkC neurotrophin receptor co-activator, LM22B-10 selectively activates TrkB, TrkC, AKT and ERK in vivo and in vitro. |
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S7745 |
ANA-12ANA-12 is a selective TrkB antagonist with Kd of 10 nM and 12 μM for the high and low affinity sites, respectively. |
Maternal exercise ameliorated sevoflurane-induced neuronal cell loss and decreased dendritic spine density, blocked by TrkB inhibition. Nissl staining and Golgi staining were performed after behavior tests (n = 3). (A) Nissl staining in the CA1 region of hippocampus under ×400. (B) Neuronal density ratio changes. (C) Golgi staining in the CA1 of hippocampus under ×1000. (D) Histograms represented the number of dendritic spines/10 μm. Values are mean ± S.E.M. *p < 0.05, compared with Ctrl group; **p < 0.01, compared with Ctrl group; ##p < 0.01, compared with Sevo group; ∧∧p < 0.01, compared with Sevo + ME group. One-way analysis of variance followed by Tukey post hoc multiple comparison tests was used for data analysis.
|
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S0827New |
LM 22A4LM22A-4 is a specific agonist of tyrosine kinase receptor B (TrkB) with IC50 of 47 nM. LM22A-4 is used for neurological disease research. |
||
| S8319 |
7,8-Dihydroxyflavone7,8-Dihydroxyflavone (7,8-DHF) 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). |
