S1012 |
BMS-536924
|
BMS-536924 (CS-0117) is an ATP-competitive IGF-1R/IR inhibitor with IC50 of 100 nM/73 nM, modest activity for Mek, Fak, and Lck with very little activity for Akt1, MAPK1/2. |
-
Elife, 2022, 11e76183
-
Oral Dis, 2021, 27(2):290-300
-
Mol Neurobiol, 2020, 57(3):1570-1593
|
|
S1034 |
NVP-AEW541
|
NVP-AEW541 is a potent inhibitor of IGF-1R/InsR with IC50 of 150 nM/140 nM in cell-free assays, greater potency and selectivity for IGF-1R in a cell-based assay. |
-
Toxicol In Vitro, 2022, 83:105384
-
Cancer Cell, 2021, S1535-6108(21)00383-4
-
Cancer Cell, 2021, S1535-6108(21)00492-X
|
|
S1069 |
Luminespib (NVP-AUY922)
|
Luminespib (AUY-922, NVP-AUY922, VER-52296) is a highly potent HSP90 inhibitor for HSP90α/β with IC50 of 13 nM /21 nM in cell-free assays, weaker potency against the HSP90 family members GRP94 and TRAP-1, exhibits the tightest binding of any small-molecule HSP90 ligand. Luminespib (AUY-922, NVP-AUY922) effectively downregulates and destabilizes the IGF-1Rβ protein and results in growth inhibition, autophagy and apoptosis. Phase 2. |
-
Biomedicines, 2022, 10(3)624
-
Cell Death Discov, 2022, 8(1):86
-
Cell Rep, 2021, 34(11):108870
|
|
S1088 |
NVP-ADW742
|
NVP-ADW742 (GSK 552602A) is an IGF-1R inhibitor with IC50 of 0.17 μM, >16-fold more potent against IGF-1R than InsR; little activity to HER2, PDGFR, VEGFR-2, Bcr-Abl and c-Kit. |
-
Nat Chem Biol, 2022, 10.1038/s41589-022-00996-7
-
Head Neck, 2022, 44(5):1192-1205
-
Cancer Biomark, 2021, 10.3233/CBM-210016
|
|
S1091 |
Linsitinib (OSI-906)
|
Linsitinib (OSI-906) is a selective inhibitor of IGF-1R with IC50 of 35 nM in cell-free assays; modestly potent to InsR with IC50 of 75 nM, and no activity towards Abl, ALK, BTK, EGFR, FGFR1/2, PKA etc. Phase 3. |
-
Nat Commun, 2022, 13(1):684
-
Nat Commun, 2022, 13(1):2500
-
Nat Chem Biol, 2022, 10.1038/s41589-022-00996-7
|
|
S1093 |
GSK1904529A
|
GSK1904529A (GSK 4529) is a selective inhibitor of IGF-1R and IR with IC50 of 27 nM and 25 nM in cell-free assays, >100-fold more selective for IGF-1R/InsR than Akt1/2, Aurora A/B,B-Raf, CDK2, EGFR etc. |
-
Biomolecules, 2022, 12(4)563
-
Life Sci, 2021, 270:118980
-
Biol Reprod, 2020, 102(1):116-132
|
|
S1124 |
BMS-754807
|
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 (c-Met), Aurora A/B, TrkA/B and Ron, and shows little activity to Flt3, Lck, MK2, PKA, PKC etc. Phase 2. |
-
Front Oncol, 2021, 11:650052
-
Life Sci, 2021, 267:118977
-
Sci China Life Sci, 2021, 10.1007/s11427-020-1836-7
|
|
S1234 |
AG-1024
|
AG-1024 (Tyrphostin, AGS 200) inhibits IGF-1R autophosphorylation with IC50 of 7 μM, is less potent to IR with IC50 of 57 μM and specifically distinguishes between InsR and IGF-1R (as compared to other tyrphostins). |
-
Pharmaceuticals (Basel), 2022, 15(2)241
-
PLoS One, 2021, 16(2):e0247190
-
J Hematol Oncol, 2020, 13(1):77
|
|
S1272 |
XL228
|
XL228 is a protein kinase inhibitor with IC50 of 5 nM, 1.4 nM, 3.1 nM, 1.6 nM, 6.1 nM and 2 nM for wild-type ABL kinase, ABL T315I, Aurora A, IGF-1R, SRC and LYN, respectively. |
|
|
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. |
-
Cancer Cell, 2021, S1535-6108(21)00383-4
-
J Invest Dermatol, 2020, 3 pii: S0022-202X(20)31407-X
-
Cell, 2019, 36(2):179-193
|
|
S3187 |
SBI-477
|
SBI-477 is an insulin signaling inhibitor that deactivates the transcription factor MondoA, leading to reduced expression of the insulin pathway suppressors thioredoxin-interacting protein (TXNIP) and arrestin domain-containing 4 (ARRDC4). SBI-477 inhibits triacylglyceride (TAG) synthesis and enhances basal glucose uptake in human skeletal myocytes. |
|
|
S3984 |
Nordihydroguaiaretic acid (NDGA)
|
Nordihydroguaiaretic acid (NDGA) is a phenolic antioxidant found in the leaves and twigs of the evergreen desert shrub, Larrea tridentata (Sesse and Moc. ex DC) Coville (creosote bush). It is a recognized inhibitor of lipoxygenase (LOX) and has antioxidant and free radical scavenging properties. Nordihydroguaiaretic acid (NDGA) is a cytotoxic insulin-like growth factor-I receptor (IGF-1R)/HER2 inhibitor and induces apoptosis. Nordihydroguaiaretic acid (NDGA) inhibits p300 and activates autophagy. Nordihydroguaiaretic acid (NDGA) protects cells from ferroptosis. |
|
|
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. |
-
Cancer Res, 2022, 82(2):307-319
-
NPJ Precis Oncol, 2022, 6(1):11
-
Nature, 2021, 600(7888):319-323
|
|
S7083 |
Ceritinib (LDK378)
|
Ceritinib (LDK378) is 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 Res, 2022, 82(2):307-319
-
NPJ Precis Oncol, 2022, 6(1):11
-
Sci Rep, 2022, 12(1):6345
|
|
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. |
-
Cancers (Basel), 2020, 12(9)E2668
-
Aging (Albany NY), 2020, 7;12(9):8221-8240
-
Burns Trauma, 2020, 8:tkaa025
|
|
S7668 |
Picropodophyllin (PPP)
|
Picropodophyllin (PPP, AXL1717) is a IGF-1R inhibitor with IC50 of 1 nM. It displays selectivity for IGF-1R and does not coinhibit tyrosine phosphorylation the IR, or of a selected panel of receptors less related to IGF-IR(FGF-R, PDGF-R, OR EGF-R). Picropodophyllin (PPP) induces apoptosis with antineoplastic activity. |
-
Ann Neurol, 2022, 10.1002/ana.26383
-
Cell Rep, 2022, 39(1):110608
-
Transl Lung Cancer Res, 2022, 11(4):543-559
|
|
S8003 |
PQ 401
|
PQ401 inhibits autophosphorylation of IGF-1R domain with IC50 of <1 μM. |
-
Acta Pharmacol Sin, 2018, 39(12):1894-1901
-
J Chemother, 2016, 28(1):44-9
-
Lung Cancer, 2015, 90(2):175-81
|
|
S8228 |
NT157
|
NT157, a selective inhibitor of IRS-1/2(insulin receptor substrate), has the potential to inhibit IGF-1R and STAT3 signaling pathways in cancer cells and stroma cells of TME leading to a decrease in cancer cell survival. |
-
Biochim Biophys Acta Mol Cell Res, 2021, 1868(1):118877
-
PLoS One, 2021, 16(2):e0247190
-
Technol Cancer Res Treat, 2021, 20:15330338211027916
|
|
S8229 |
Brigatinib (AP26113)
|
Brigatinib (AP26113) 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. |
-
NPJ Precis Oncol, 2022, 6(1):11
-
NPJ Precis Oncol, 2022, 6(1):5
-
Mol Pharmacol, 2022, MOLPHARM-AR-2021-000287
|
|
S6922 |
S961
|
S961 is a biosynthetic insulin receptor antagonist that inhibits cellular proliferation and colony formation in breast tumour cells. |
|
|
E0939New |
Insulin Degludec
|
Insulin degludec is an acylated basal insulin with a unique mechanism of protracted absorption involving the formation of a depot of soluble multihexamer chains after subcutaneous injection, shows a very long duration of action, with a half-life exceeding 25 h in PK/PD studies. |
|
|
S6955 |
Insulin (human)
|
Insulin (human) (Insulin regular) is a polypeptide hormone that regulates the level of glucose. Insulin is commonly used to treat hyperglycemia in patients with diabetes. Potency: 29 units/mg. |
-
Cell Death Dis, 2022, 13(4):351
-
Biol Pharm Bull, 2022, 45(5):614-624
-
J Virol, 2021, JVI0155021
|
|
S7453 |
MSDC-0160
|
MSDC-0160 (CAY10415) is a prototype mTOT-modulating insulin sensitizer being studied to treat diabetes and Alzheimer's disease. Phase 2. |
|
|
S1012 |
BMS-536924
|
BMS-536924 (CS-0117) is an ATP-competitive IGF-1R/IR inhibitor with IC50 of 100 nM/73 nM, modest activity for Mek, Fak, and Lck with very little activity for Akt1, MAPK1/2. |
- Elife, 2022, 11e76183
- Oral Dis, 2021, 27(2):290-300
- Mol Neurobiol, 2020, 57(3):1570-1593
|
|
S1034 |
NVP-AEW541
|
NVP-AEW541 is a potent inhibitor of IGF-1R/InsR with IC50 of 150 nM/140 nM in cell-free assays, greater potency and selectivity for IGF-1R in a cell-based assay. |
- Toxicol In Vitro, 2022, 83:105384
- Cancer Cell, 2021, S1535-6108(21)00383-4
- Cancer Cell, 2021, S1535-6108(21)00492-X
|
|
S1069 |
Luminespib (NVP-AUY922)
|
Luminespib (AUY-922, NVP-AUY922, VER-52296) is a highly potent HSP90 inhibitor for HSP90α/β with IC50 of 13 nM /21 nM in cell-free assays, weaker potency against the HSP90 family members GRP94 and TRAP-1, exhibits the tightest binding of any small-molecule HSP90 ligand. Luminespib (AUY-922, NVP-AUY922) effectively downregulates and destabilizes the IGF-1Rβ protein and results in growth inhibition, autophagy and apoptosis. Phase 2. |
- Biomedicines, 2022, 10(3)624
- Cell Death Discov, 2022, 8(1):86
- Cell Rep, 2021, 34(11):108870
|
|
S1088 |
NVP-ADW742
|
NVP-ADW742 (GSK 552602A) is an IGF-1R inhibitor with IC50 of 0.17 μM, >16-fold more potent against IGF-1R than InsR; little activity to HER2, PDGFR, VEGFR-2, Bcr-Abl and c-Kit. |
- Nat Chem Biol, 2022, 10.1038/s41589-022-00996-7
- Head Neck, 2022, 44(5):1192-1205
- Cancer Biomark, 2021, 10.3233/CBM-210016
|
|
S1091 |
Linsitinib (OSI-906)
|
Linsitinib (OSI-906) is a selective inhibitor of IGF-1R with IC50 of 35 nM in cell-free assays; modestly potent to InsR with IC50 of 75 nM, and no activity towards Abl, ALK, BTK, EGFR, FGFR1/2, PKA etc. Phase 3. |
- Nat Commun, 2022, 13(1):684
- Nat Commun, 2022, 13(1):2500
- Nat Chem Biol, 2022, 10.1038/s41589-022-00996-7
|
|
S1093 |
GSK1904529A
|
GSK1904529A (GSK 4529) is a selective inhibitor of IGF-1R and IR with IC50 of 27 nM and 25 nM in cell-free assays, >100-fold more selective for IGF-1R/InsR than Akt1/2, Aurora A/B,B-Raf, CDK2, EGFR etc. |
- Biomolecules, 2022, 12(4)563
- Life Sci, 2021, 270:118980
- Biol Reprod, 2020, 102(1):116-132
|
|
S1124 |
BMS-754807
|
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 (c-Met), Aurora A/B, TrkA/B and Ron, and shows little activity to Flt3, Lck, MK2, PKA, PKC etc. Phase 2. |
- Front Oncol, 2021, 11:650052
- Life Sci, 2021, 267:118977
- Sci China Life Sci, 2021, 10.1007/s11427-020-1836-7
|
|
S1234 |
AG-1024
|
AG-1024 (Tyrphostin, AGS 200) inhibits IGF-1R autophosphorylation with IC50 of 7 μM, is less potent to IR with IC50 of 57 μM and specifically distinguishes between InsR and IGF-1R (as compared to other tyrphostins). |
- Pharmaceuticals (Basel), 2022, 15(2)241
- PLoS One, 2021, 16(2):e0247190
- J Hematol Oncol, 2020, 13(1):77
|
|
S1272 |
XL228
|
XL228 is a protein kinase inhibitor with IC50 of 5 nM, 1.4 nM, 3.1 nM, 1.6 nM, 6.1 nM and 2 nM for wild-type ABL kinase, ABL T315I, Aurora A, IGF-1R, SRC and LYN, respectively. |
|
|
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. |
- Cancer Cell, 2021, S1535-6108(21)00383-4
- J Invest Dermatol, 2020, 3 pii: S0022-202X(20)31407-X
- Cell, 2019, 36(2):179-193
|
|
S3187 |
SBI-477
|
SBI-477 is an insulin signaling inhibitor that deactivates the transcription factor MondoA, leading to reduced expression of the insulin pathway suppressors thioredoxin-interacting protein (TXNIP) and arrestin domain-containing 4 (ARRDC4). SBI-477 inhibits triacylglyceride (TAG) synthesis and enhances basal glucose uptake in human skeletal myocytes. |
|
|
S3984 |
Nordihydroguaiaretic acid (NDGA)
|
Nordihydroguaiaretic acid (NDGA) is a phenolic antioxidant found in the leaves and twigs of the evergreen desert shrub, Larrea tridentata (Sesse and Moc. ex DC) Coville (creosote bush). It is a recognized inhibitor of lipoxygenase (LOX) and has antioxidant and free radical scavenging properties. Nordihydroguaiaretic acid (NDGA) is a cytotoxic insulin-like growth factor-I receptor (IGF-1R)/HER2 inhibitor and induces apoptosis. Nordihydroguaiaretic acid (NDGA) inhibits p300 and activates autophagy. Nordihydroguaiaretic acid (NDGA) protects cells from ferroptosis. |
|
|
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. |
- Cancer Res, 2022, 82(2):307-319
- NPJ Precis Oncol, 2022, 6(1):11
- Nature, 2021, 600(7888):319-323
|
|
S7083 |
Ceritinib (LDK378)
|
Ceritinib (LDK378) is 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 Res, 2022, 82(2):307-319
- NPJ Precis Oncol, 2022, 6(1):11
- Sci Rep, 2022, 12(1):6345
|
|
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. |
- Cancers (Basel), 2020, 12(9)E2668
- Aging (Albany NY), 2020, 7;12(9):8221-8240
- Burns Trauma, 2020, 8:tkaa025
|
|
S7668 |
Picropodophyllin (PPP)
|
Picropodophyllin (PPP, AXL1717) is a IGF-1R inhibitor with IC50 of 1 nM. It displays selectivity for IGF-1R and does not coinhibit tyrosine phosphorylation the IR, or of a selected panel of receptors less related to IGF-IR(FGF-R, PDGF-R, OR EGF-R). Picropodophyllin (PPP) induces apoptosis with antineoplastic activity. |
- Ann Neurol, 2022, 10.1002/ana.26383
- Cell Rep, 2022, 39(1):110608
- Transl Lung Cancer Res, 2022, 11(4):543-559
|
|
S8003 |
PQ 401
|
PQ401 inhibits autophosphorylation of IGF-1R domain with IC50 of <1 μM. |
- Acta Pharmacol Sin, 2018, 39(12):1894-1901
- J Chemother, 2016, 28(1):44-9
- Lung Cancer, 2015, 90(2):175-81
|
|
S8228 |
NT157
|
NT157, a selective inhibitor of IRS-1/2(insulin receptor substrate), has the potential to inhibit IGF-1R and STAT3 signaling pathways in cancer cells and stroma cells of TME leading to a decrease in cancer cell survival. |
- Biochim Biophys Acta Mol Cell Res, 2021, 1868(1):118877
- PLoS One, 2021, 16(2):e0247190
- Technol Cancer Res Treat, 2021, 20:15330338211027916
|
|
S8229 |
Brigatinib (AP26113)
|
Brigatinib (AP26113) 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. |
- NPJ Precis Oncol, 2022, 6(1):11
- NPJ Precis Oncol, 2022, 6(1):5
- Mol Pharmacol, 2022, MOLPHARM-AR-2021-000287
|
|