S1068 |
Crizotinib
|
Crizotinib is a potent inhibitor of c-Met and ALK with IC50 of 11 nM and 24 nM in cell-based assays, respectively. It is also a potent ROS1 inhibitor with Ki value less than 0.025 nM. Crizotinib induces autophagy through inhibition of the STAT3 pathway in multiple lung cancer cell lines. |
-
Cancer Discov, 2024, OF1-OF20.
-
Nat Commun, 2024, 15(1):1009
-
Nat Commun, 2024, 15(1):51
|
|
S7083 |
Ceritinib
|
Ceritinib is a potent inhibitor against ALK with IC50 of 0.2 nM in cell-free assays. Ceritinib (LDK378) also inhibits IGF-1R, InsR, STK22D and FLT3 with IC50 of 8 nM, 7 nM, 23 nM and 60 nM, respectively. Phase 3. |
-
Cancer Discov, 2024, OF1-OF20.
-
Nat Commun, 2024, 15(1):51
-
Commun Biol, 2024, 7(1):412
|
|
S1108 |
TAE684 (NVP-TAE684)
|
TAE684 (NVP-TAE684) is a potent and selective ALK inhibitor which blocked the growth of ALCL-derived and ALK-dependent cell lines with IC50 values between 2 and 10 nM, 100-fold more sensitive for ALK than InsR. TAE684 (NVP-TAE684) induces cell cycle arrest and apoptosis. |
-
Sci Rep, 2024, 14(1):8200
-
EMBO Rep, 2023, 24(7):e56937
-
J Biol Chem, 2023, 299(6):104825
|
|
S2762 |
Alectinib
|
Alectinib is a potent ALK inhibitor with IC50 of 1.9 nM in cell-free assays, sensitive to L1196M mutation and higher selectivity for ALK than PF-02341066, NVP-TAE684 and PHA-E429. |
-
Cancer Discov, 2024, OF1-OF20.
-
Nat Commun, 2024, 15(1):3741
-
Nat Commun, 2024, 15(1):9473
|
|
S5190 |
Crizotinib hydrochloride
|
Crizotinib (PF-02341066) hydrochloride (Xalkori) inhibits tyrosine phosphorylation of c-Met and nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) with IC50 of of 11 nM and 24 nM in cell-based assays, respectively. Crizotinib hydrochloride is also a potent ROS1 inhibitor with Ki less than 0.025 nM. Crizotinib induces autophagy through inhibition of the STAT3 pathway in multiple lung cancer cell lines. |
-
Cancer Discov, 2023, 13(3):598-615
-
Nat Commun, 2023, 14(1):2829
-
Cancer Res Commun, 2023, 3(4):659-671
|
|
S7536 |
Lorlatinib (PF-6463922)
|
Lorlatinib (PF-6463922) is a potent, dual ALK/ROS1 inhibitor with Ki of <0.02 nM, <0.07 nM, and 0.7 nM for ROS1, ALK (WT), and ALK (L1196M), respectively. PF-06463922 induces apoptosis. Phase 1. |
-
Cancer Discov, 2024, OF1-OF20.
-
Commun Biol, 2024, 7(1):412
-
Transl Lung Cancer Res, 2024, 13(2):321-333
|
|
S7998 |
Entrectinib
|
Entrectinib 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. |
-
Signal Transduct Target Ther, 2024, 9(1):153
-
Biomed Pharmacother, 2024, 176:116766
-
J Pathol, 2024, 263(2):257-269
|
|
S8229 |
Brigatinib
|
Brigatinib is a potent and selective ALK (IC50, 0.6 nM) and ROS1 (IC50, 0.9 nM) inhibitor. It also inhibits IGF-1R, FLT3, and mutant variants of FLT3 (D835Y) and EGFR with lower potentcy. |
-
Cancer Discov, 2024, OF1-OF20.
-
Commun Biol, 2024, 7(1):412
-
Sci Rep, 2024, 14(1):8200
|
|
S5232 |
Alectinib (CH5424802) hydrochloride
|
Alectinib (AF802, CH5424802, RO5424802, RG-7853) is a second generation oral drug that selectively inhibits the activity of anaplastic lymphoma kinase (ALK) tyrosine kinase. |
-
Biomolecules, 2023, 13(3)438
-
Exp Mol Med, 2022, 54(8):1225-1235
-
NPJ Precis Oncol, 2022, 6(1):5
|
|
S2703 |
GSK1838705A
|
GSK1838705A is a potent IGF-1R inhibitor with IC50 of 2.0 nM, modestly potent to IR and ALK with IC50 of 1.6 nM and 0.5 nM, respectively, and little activity to other protein kinases. |
-
Sci Signal, 2022, 15(747):eabj5879
-
Cancer Cell, 2021, S1535-6108(21)00383-4
-
J Invest Dermatol, 2020, 3 pii: S0022-202X(20)31407-X
|
|
S4967 |
Ceritinib dihydrochloride
|
Ceritinib (Zykadia, LDK378) dihydrochloride is a selective, orally bioavailable and ATP-competitive inhibitor of ALK with IC50 of 0.2 nM. Ceritinib dihydrochloride also inhibits InsR, IGF-1R and STK22D with IC50 of 7 nM, 8 nM and 23 nM, respectively. Ceritinib exhibits antitomor activity. |
-
Exp Mol Med, 2022, 54(8):1225-1235
-
Cancer Res, 2022, 82(2):307-319
-
NPJ Precis Oncol, 2022, 6(1):11
|
|
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). |
-
Commun Biol, 2024, 7(1):412
-
Cancer Discov, 2023, 13(3):598-615
-
EMBO Mol Med, 2023, 10.15252/emmm.202217367
|
|
S7106 |
AZD3463
|
AZD3463 is a novel orally bioavailable ALK inhibitor with Ki of 0.75 nM, which also inhibits IGF1R with equivalent potency. AZD3463 suppresses cell viability by inducing both cell apoptosis and autophagy. |
-
Sci Rep, 2024, 14(1):8200
-
bioRxiv, 2023, 10.1101/2023.12.19.572304
-
Burns Trauma, 2020, 8:tkaa025
|
|
S7000 |
AP26113-analog (ALK-IN-1)
|
AP26113-analog (ALK-IN-1) is an analog of AP26113 which is a potent and selective ALK inhibitor. It is also an inhibitor of EGFR. |
-
Clin Cancer Res, 2015, 21(1):166-74
-
Clin Cancer Res, 2014, 20(22):5686-96
-
Clin Cancer Res, 2014, 20(22):5686-96
|
|
S8054 |
ASP3026
|
ASP3026 is a novel and selective inhibitor for ALK with IC50 of 3.5 nM. Phase 1. |
-
Cell Rep, 2021, 36(7):109515
-
Invest New Drugs, 2019, 10.1007/s10637-019-00802-7
-
Mol Cancer Ther, 2018, 17(1):222-231
|
|
S2934 |
Ensartinib dihydrochloride
|
Ensartinib dihydrochloride is a potent new-generation ALK inhibitor with high activity against a broad range of known crizotinib-resistant ALK mutations and CNS metastases. It potently inhibits both wild-type ALK and ALK variants (F1174, C1156Y, L1196M, S1206R, T1151, and G1202R mutants) with in vitro IC50s of <4 nM. |
-
Cancer Discov, 2024, OF1-OF20.
-
Biol Reprod, 2024, ioae090
-
Biomed Pharmacother, 2022, 158:114162
|
|
S6513 |
HG-14-10-04
|
HG-14-10-04 is an inhibitor of ALK. |
|
|
S6505 |
X-376
|
X-376 is an ALK inhibitor and potentially useful in non-small cell lung cancer. |
|
|
E2836 |
ALK inhibitor 1
|
ALK inhibitor 1 (compound 17) is a potent pyrimidin ALK inhibitor which can inhibit testis-specific serine/threonine kinase (TSSK2; IC50=31 nM) and focal adhesion kinase (FAK; IC50=2 nM). |
|
|
E1846New |
TL13-112
|
TL13-112 is a degrader of anaplastic lymphoma kinase (ALK) with an IC50 of 0.60 nM. It demonstrates anti-proliferative activity in non-small-cell lung cancer (NSCLC) and anaplastic large cell lymphoma (ALCL) cell lines. |
|
|
E1508New |
APG-2449
|
APG-2449 is an orally active inhibitor of ALK/ROS1/FAK. APG-2449 exerts potent and durable antitumor activity in human non-small-cell lung cancer (NSCLC) and ovarian tumor models. |
|
|
E1865New |
Envonalkib
|
Envonalkib(TQ-B3139, CT-71, Formula 1) is a potent and orally active inhibitor of ALK, that exhibits IC50 values of 1.96 nM, 35.1 nM, and 61.3 nM for wild-type and mutated L1196M and G1269S-ALK. Envonalkib is also used in the research of non-small cell lung cancer. |
|
|
E1961New |
NVL-655
|
NVL-655 is a selective inhibitor of anaplastic lymphoma kinase (ALK), with potential antineoplastic activity in the Ba/F3 xenograft model. It also exhibits significant inhibitory activity against ROS1, LTK, PYK2, TRKB, and FAK, with an IC50 ≤10-fold ALK and demonstrates high potency against specific ALK mutations, with an IC50 of <0.73 nM, 7 nM, 3 nM, 3 nM for G1202R, G1202R/L1196M, G1202R/G1269A and G1202R/L1198F respectively. |
|
|
E1783New |
Conteltinib(CT-707)
|
Conteltinib(CT-707) is a potent multikinase inhibitor of ALK, FAK,Pyk2, showing promising anti-tumor activities. Conteltinib exhibits significant inhibitory effects on FAK with an IC50 value of 1.6 nM in vitro kinase assay. |
|
|
A2621 |
Anti-ACVR1 / ALK-2 (DS-6016a)
|
Anti-ACVR1 / ALK-2 (DS-6016a) monoclonal antibody targeting ALK-2. It can be used in the treatment of fibrodysplasia ossificans progressiva (FOP). MW :145.56. |
|
|
E1565New |
Iruplinalkib
|
Iruplinalkib (WX-0593) is a highly selective oral inhibitor of ALK and ROS1 tyrosine kinase. It exhibits potent and promising antitumor activity in advanced non-small cell lung cancer (NSCLC) with ALK or ROS1 rearrangement. |
|
|
S0072 |
MS4078
|
MS4078 is an inhibitor and PROTAC (degrader) of ALK. MS4078 reduces the NPM-ALK protein levels in SU-DHL-1 cells and the EML4-ALK protein levels in NCI-H2228 cells with DC50 of 11 nM and 59 nM, respectively. MS4078 induces ALK protein degradation via cereblon and proteasome dependent mechanism and potently inhibits proliferation of SU-DHL-1 cells with IC50 of 33 nM. |
|
|
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).
"
|
|
|
E1507 |
Zilurgisertib fumarate
|
Zilurgisertib fumarate(INCB-000928 fumarate, NBU-928 fumarate) is a selective ALK 2 inhibitor.It is under development for the treatment of heterotopic ossification and fibrodysplasia ossificans progressiva. |
|
|
E1732 |
Itacnosertib (TP-0184)
|
Itacnosertib (TP-0184) is a small-molecule inhibitor of the BMP type 1 receptor ALK2 (also known as ACVR1). Itacnosertib reduces hepcidin induction and elevated serum iron levels in turpentine and lung cancer mouse models of ACD. |
|
|
A2594 |
Ascrinvacumab (Anti-ACVRL1 / ALK-1)
|
Ascrinvacumab (Anti-ACVRL1 / ALK-1) is a human IgG2 monoclonal antibody targeting ALK-1. It can be used for the treatment of hepatocellular carcinoma (HCC), in patients with advanced solid tumors. It also demonstrates its use in antiangiogenic therapy. MW : 150 KD. |
|
|
E0958 |
ZX-29
|
ZX-29 is a potent and selective ALK inhibitor with an IC50s of 2.1, 1.3 and 3.9 nM for ALK, ALK L1196M and ALK G1202R mutations, respectively. |
|
|
S1068 |
Crizotinib
|
Crizotinib is a potent inhibitor of c-Met and ALK with IC50 of 11 nM and 24 nM in cell-based assays, respectively. It is also a potent ROS1 inhibitor with Ki value less than 0.025 nM. Crizotinib induces autophagy through inhibition of the STAT3 pathway in multiple lung cancer cell lines. |
- Cancer Discov, 2024, OF1-OF20.
- Nat Commun, 2024, 15(1):1009
- Nat Commun, 2024, 15(1):51
|
|
S7083 |
Ceritinib
|
Ceritinib is a potent inhibitor against ALK with IC50 of 0.2 nM in cell-free assays. Ceritinib (LDK378) also inhibits IGF-1R, InsR, STK22D and FLT3 with IC50 of 8 nM, 7 nM, 23 nM and 60 nM, respectively. Phase 3. |
- Cancer Discov, 2024, OF1-OF20.
- Nat Commun, 2024, 15(1):51
- Commun Biol, 2024, 7(1):412
|
|
S1108 |
TAE684 (NVP-TAE684)
|
TAE684 (NVP-TAE684) is a potent and selective ALK inhibitor which blocked the growth of ALCL-derived and ALK-dependent cell lines with IC50 values between 2 and 10 nM, 100-fold more sensitive for ALK than InsR. TAE684 (NVP-TAE684) induces cell cycle arrest and apoptosis. |
- Sci Rep, 2024, 14(1):8200
- EMBO Rep, 2023, 24(7):e56937
- J Biol Chem, 2023, 299(6):104825
|
|
S2762 |
Alectinib
|
Alectinib is a potent ALK inhibitor with IC50 of 1.9 nM in cell-free assays, sensitive to L1196M mutation and higher selectivity for ALK than PF-02341066, NVP-TAE684 and PHA-E429. |
- Cancer Discov, 2024, OF1-OF20.
- Nat Commun, 2024, 15(1):3741
- Nat Commun, 2024, 15(1):9473
|
|
S5190 |
Crizotinib hydrochloride
|
Crizotinib (PF-02341066) hydrochloride (Xalkori) inhibits tyrosine phosphorylation of c-Met and nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) with IC50 of of 11 nM and 24 nM in cell-based assays, respectively. Crizotinib hydrochloride is also a potent ROS1 inhibitor with Ki less than 0.025 nM. Crizotinib induces autophagy through inhibition of the STAT3 pathway in multiple lung cancer cell lines. |
- Cancer Discov, 2023, 13(3):598-615
- Nat Commun, 2023, 14(1):2829
- Cancer Res Commun, 2023, 3(4):659-671
|
|
S7536 |
Lorlatinib (PF-6463922)
|
Lorlatinib (PF-6463922) is a potent, dual ALK/ROS1 inhibitor with Ki of <0.02 nM, <0.07 nM, and 0.7 nM for ROS1, ALK (WT), and ALK (L1196M), respectively. PF-06463922 induces apoptosis. Phase 1. |
- Cancer Discov, 2024, OF1-OF20.
- Commun Biol, 2024, 7(1):412
- Transl Lung Cancer Res, 2024, 13(2):321-333
|
|
S7998 |
Entrectinib
|
Entrectinib 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. |
- Signal Transduct Target Ther, 2024, 9(1):153
- Biomed Pharmacother, 2024, 176:116766
- J Pathol, 2024, 263(2):257-269
|
|
S8229 |
Brigatinib
|
Brigatinib is a potent and selective ALK (IC50, 0.6 nM) and ROS1 (IC50, 0.9 nM) inhibitor. It also inhibits IGF-1R, FLT3, and mutant variants of FLT3 (D835Y) and EGFR with lower potentcy. |
- Cancer Discov, 2024, OF1-OF20.
- Commun Biol, 2024, 7(1):412
- Sci Rep, 2024, 14(1):8200
|
|
S5232 |
Alectinib (CH5424802) hydrochloride
|
Alectinib (AF802, CH5424802, RO5424802, RG-7853) is a second generation oral drug that selectively inhibits the activity of anaplastic lymphoma kinase (ALK) tyrosine kinase. |
- Biomolecules, 2023, 13(3)438
- Exp Mol Med, 2022, 54(8):1225-1235
- NPJ Precis Oncol, 2022, 6(1):5
|
|
S2703 |
GSK1838705A
|
GSK1838705A is a potent IGF-1R inhibitor with IC50 of 2.0 nM, modestly potent to IR and ALK with IC50 of 1.6 nM and 0.5 nM, respectively, and little activity to other protein kinases. |
- Sci Signal, 2022, 15(747):eabj5879
- Cancer Cell, 2021, S1535-6108(21)00383-4
- J Invest Dermatol, 2020, 3 pii: S0022-202X(20)31407-X
|
|
S4967 |
Ceritinib dihydrochloride
|
Ceritinib (Zykadia, LDK378) dihydrochloride is a selective, orally bioavailable and ATP-competitive inhibitor of ALK with IC50 of 0.2 nM. Ceritinib dihydrochloride also inhibits InsR, IGF-1R and STK22D with IC50 of 7 nM, 8 nM and 23 nM, respectively. Ceritinib exhibits antitomor activity. |
- Exp Mol Med, 2022, 54(8):1225-1235
- Cancer Res, 2022, 82(2):307-319
- NPJ Precis Oncol, 2022, 6(1):11
|
|
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). |
- Commun Biol, 2024, 7(1):412
- Cancer Discov, 2023, 13(3):598-615
- EMBO Mol Med, 2023, 10.15252/emmm.202217367
|
|
S7106 |
AZD3463
|
AZD3463 is a novel orally bioavailable ALK inhibitor with Ki of 0.75 nM, which also inhibits IGF1R with equivalent potency. AZD3463 suppresses cell viability by inducing both cell apoptosis and autophagy. |
- Sci Rep, 2024, 14(1):8200
- bioRxiv, 2023, 10.1101/2023.12.19.572304
- Burns Trauma, 2020, 8:tkaa025
|
|
S7000 |
AP26113-analog (ALK-IN-1)
|
AP26113-analog (ALK-IN-1) is an analog of AP26113 which is a potent and selective ALK inhibitor. It is also an inhibitor of EGFR. |
- Clin Cancer Res, 2015, 21(1):166-74
- Clin Cancer Res, 2014, 20(22):5686-96
- Clin Cancer Res, 2014, 20(22):5686-96
|
|
S8054 |
ASP3026
|
ASP3026 is a novel and selective inhibitor for ALK with IC50 of 3.5 nM. Phase 1. |
- Cell Rep, 2021, 36(7):109515
- Invest New Drugs, 2019, 10.1007/s10637-019-00802-7
- Mol Cancer Ther, 2018, 17(1):222-231
|
|
S2934 |
Ensartinib dihydrochloride
|
Ensartinib dihydrochloride is a potent new-generation ALK inhibitor with high activity against a broad range of known crizotinib-resistant ALK mutations and CNS metastases. It potently inhibits both wild-type ALK and ALK variants (F1174, C1156Y, L1196M, S1206R, T1151, and G1202R mutants) with in vitro IC50s of <4 nM. |
- Cancer Discov, 2024, OF1-OF20.
- Biol Reprod, 2024, ioae090
- Biomed Pharmacother, 2022, 158:114162
|
|
S6513 |
HG-14-10-04
|
HG-14-10-04 is an inhibitor of ALK. |
|
|
S6505 |
X-376
|
X-376 is an ALK inhibitor and potentially useful in non-small cell lung cancer. |
|
|
E2836 |
ALK inhibitor 1
|
ALK inhibitor 1 (compound 17) is a potent pyrimidin ALK inhibitor which can inhibit testis-specific serine/threonine kinase (TSSK2; IC50=31 nM) and focal adhesion kinase (FAK; IC50=2 nM). |
|
|
E1508New |
APG-2449
|
APG-2449 is an orally active inhibitor of ALK/ROS1/FAK. APG-2449 exerts potent and durable antitumor activity in human non-small-cell lung cancer (NSCLC) and ovarian tumor models. |
|
|
E1865New |
Envonalkib
|
Envonalkib(TQ-B3139, CT-71, Formula 1) is a potent and orally active inhibitor of ALK, that exhibits IC50 values of 1.96 nM, 35.1 nM, and 61.3 nM for wild-type and mutated L1196M and G1269S-ALK. Envonalkib is also used in the research of non-small cell lung cancer. |
|
|
E1961New |
NVL-655
|
NVL-655 is a selective inhibitor of anaplastic lymphoma kinase (ALK), with potential antineoplastic activity in the Ba/F3 xenograft model. It also exhibits significant inhibitory activity against ROS1, LTK, PYK2, TRKB, and FAK, with an IC50 ≤10-fold ALK and demonstrates high potency against specific ALK mutations, with an IC50 of <0.73 nM, 7 nM, 3 nM, 3 nM for G1202R, G1202R/L1196M, G1202R/G1269A and G1202R/L1198F respectively. |
|
|
E1783New |
Conteltinib(CT-707)
|
Conteltinib(CT-707) is a potent multikinase inhibitor of ALK, FAK,Pyk2, showing promising anti-tumor activities. Conteltinib exhibits significant inhibitory effects on FAK with an IC50 value of 1.6 nM in vitro kinase assay. |
|
|
E1565New |
Iruplinalkib
|
Iruplinalkib (WX-0593) is a highly selective oral inhibitor of ALK and ROS1 tyrosine kinase. It exhibits potent and promising antitumor activity in advanced non-small cell lung cancer (NSCLC) with ALK or ROS1 rearrangement. |
|
|
S0072 |
MS4078
|
MS4078 is an inhibitor and PROTAC (degrader) of ALK. MS4078 reduces the NPM-ALK protein levels in SU-DHL-1 cells and the EML4-ALK protein levels in NCI-H2228 cells with DC50 of 11 nM and 59 nM, respectively. MS4078 induces ALK protein degradation via cereblon and proteasome dependent mechanism and potently inhibits proliferation of SU-DHL-1 cells with IC50 of 33 nM. |
|
|
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).
"
|
|
|
E1507 |
Zilurgisertib fumarate
|
Zilurgisertib fumarate(INCB-000928 fumarate, NBU-928 fumarate) is a selective ALK 2 inhibitor.It is under development for the treatment of heterotopic ossification and fibrodysplasia ossificans progressiva. |
|
|
E1732 |
Itacnosertib (TP-0184)
|
Itacnosertib (TP-0184) is a small-molecule inhibitor of the BMP type 1 receptor ALK2 (also known as ACVR1). Itacnosertib reduces hepcidin induction and elevated serum iron levels in turpentine and lung cancer mouse models of ACD. |
|
|
E0958 |
ZX-29
|
ZX-29 is a potent and selective ALK inhibitor with an IC50s of 2.1, 1.3 and 3.9 nM for ALK, ALK L1196M and ALK G1202R mutations, respectively. |
|
|