Linsitinib
Names
Preferred IUPAC name
(1s ,3s )-3-[8-Amino-1-(2-phenylquinolin-7-yl)imidazo[1,5-a ]pyrazin-3-yl]-1-methylcyclobutan-1-ol
Other names
OSI-906
Identifiers
ChEBI
ChEMBL
ChemSpider
DrugBank
KEGG
UNII
InChI=1S/C26H23N5O/c1-26(32)14-19(15-26)25-30-22(23-24(27)28-11-12-31(23)25)18-8-7-17-9-10-20(29-21(17)13-18)16-5-3-2-4-6-16/h2-13,19,32H,14-15H2,1H3,(H2,27,28)
Key: PKCDDUHJAFVJJB-UHFFFAOYSA-N
InChI=1/C26H23N5O/c1-26(32)14-19(15-26)25-30-22(23-24(27)28-11-12-31(23)25)18-8-7-17-9-10-20(29-21(17)13-18)16-5-3-2-4-6-16/h2-13,19,32H,14-15H2,1H3,(H2,27,28)/t19-,26+
Key: PKCDDUHJAFVJJB-VLZXCDOPBI
C[C@]1(C[C@@H](C1)C2=NC(=C3N2C=CN=C3N)C4=CC5=C(C=CC(=N5)C6=CC=CC=C6)C=C4)O
Properties
C 26 H 23 N 5 O
Molar mass
421.504 g·mol−1
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
Chemical compound
Linsitinib is an experimental drug candidate for the treatment of various types of cancer. It is an inhibitor of the insulin receptor and of the insulin-like growth factor 1 receptor (IGF-1R).[1] This prevents tumor cell proliferation and induces tumor cell apoptosis .[2]
Linsitinib was granted orphan drug designation for adrenocortical carcinoma in March 2012.[3]
Phase II clinical trials were initiated for multiple myeloma, ovarian cancer, hepatocellular carcinoma, and NSCLC, but subsatisfactory results caused research for these indications to be discontinued.[3] A phase III clinical trial found that linsitinib did not increase survival in patients with adrenocortical carcinoma.[4] As of 2017, no clinical trials were in progress.[3]
Growth factor receptor modulators
Angiopoietin
Kinase inhibitors: Altiratinib
CE-245677
Rebastinib
CNTF EGF (ErbB)
FGF
FGFR1 FGFR2
Agonists: Ersofermin
FGF (1 , 2 (bFGF) , 3 , 4 , 5 , 6 , 7 (KGF ), 8 , 9 , 10 (KGF2) , 17 , 18 , 22 )
Palifermin
Repifermin
Selpercatinib
Sprifermin
Trafermin
Antibodies: Aprutumab
Aprutumab ixadotin
FGFR3 FGFR4 Unsorted
HGF (c-Met) IGF
IGF-1
Kinase inhibitors: BMS-754807
Linsitinib
NVP-ADW742
NVP-AEW541
OSl-906
IGF-2
Antibodies: Dusigitumab
Xentuzumab (against IGF-1 and IGF-2)
Others
Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1)
Trofinetide
LNGF (p75NTR )
Aptamers: Against NGF: RBM-004
Decoy receptors: LEVI-04 (p75NTR -Fc)
PDGF RET (GFL)
SCF (c-Kit) TGFβ Trk
TrkA
Negative allosteric modulators: VM-902A
Aptamers: Against NGF: RBM-004
Decoy receptors: ReN-1820 (TrkAd5)
TrkB
Agonists: 3,7-DHF
3,7,8,2'-THF
4'-DMA-7,8-DHF
7,3'-DHF
7,8-DHF
7,8,2'-THF
7,8,3'-THF
Amitriptyline
BDNF
BNN-20
Deoxygedunin
Deprenyl
Diosmetin
DMAQ-B1
HIOC
LM22A-4
N-Acetylserotonin
NT-3
NT-4
Norwogonin (5,7,8-THF)
R7
R13
TDP6
TrkC
VEGF Others
Additional growth factors: Adrenomedullin
Colony-stimulating factors (see here instead)
Connective tissue growth factor (CTGF)
Ephrins (A1 , A2 , A3 , A4 , A5 , B1 , B2 , B3 )
Erythropoietin (see here instead)
Glucose-6-phosphate isomerase (GPI; PGI, PHI, AMF)
Glia maturation factor (GMF)
Hepatoma-derived growth factor (HDGF)
Interleukins /T-cell growth factors (see here instead)
Leukemia inhibitory factor (LIF)
Macrophage-stimulating protein (MSP; HLP, HGFLP)
Midkine (NEGF2)
Migration-stimulating factor (MSF; PRG4)
Oncomodulin
Pituitary adenylate cyclase-activating peptide (PACAP)
Pleiotrophin
Renalase
Thrombopoietin (see here instead)
Wnt signaling proteins
Additional growth factor receptor modulators: Cerebrolysin (neurotrophin mixture)