DetailsApatinib

Identification
Chemical Name Apatinib
Accession Number HAMDB226
Alternative Names YN 968D1;YN968D1;YN-968D1
IUPAC Name N-[4-(1-cyanocyclopentyl)phenyl]-2-(pyridin-4-ylmethylamino)pyridine-3-carboxamide;methanesulfonic acid
Formula C25H27N5O4S
Canonical SMILES CS(=O)(=O)O.C1CCC(C1)(C#N)C2=CC=C(C=C2)NC(=O)C3=C(N=CC=C3)NCC4=CC=NC=C4
Structure
Physicochemical Properties
Molecular Weight 493.578Molecular weight
Hbond Donor 5Number of hydrogen bond acceptor atoms (not counting acidic atoms but counting atoms that are both hydrogen bond donors and acceptors such as -OH).
Hbond Acceptor 7 Number of hydrogen bond donor atoms (not counting basic atoms but counting atoms that are both hydrogen bond donors and acceptors such as -OH).
logP (o/w) 2.958 Log of the octanol/water partition coefficient (including implicit hydrogens). [LOGP 1998]
logS -4.330 Log of the aqueous solubility (mol/L).
MR 13.560 Molecular refractivity (including implicit hydrogens).
SlogP 3.881 Log of the octanol/water partition coefficient. [Crippen 1999]
TPSA 145.070 Polar surface area (Å2) calculated using group contributions to approximate the polar surface area from connection table information only. The parameterization is that of Ertl et al. [Ertl 2000].
logD (PH=7) 3.715 The octanol/water distribution coefficient at pH 7.
pKa (PH=7) 5.355 The pKa of the reaction that removes a proton from the ensemble of states with a hydrogen count equal to the input structure.
pKb (PH=7) 9.478 The pKb of the reaction that adds a proton from the ensemble of states with a hydrogen count equal to the input structure.
Lipinski druglike 1 One if and only if lip_violation < 2 otherwise zero.
Solubility DMSO: ≥ 32 mg/mL
Role in Autophagy
Not Available
Biological Behaviors
Gene Name KDR
Target Autophagy; VEGFR;
Pathway
  1. Autophagy
  2. Protein Tyrosine Kinase/RTK
Biological Description Apatinib(YN-968D1) is an orally bioavailable, selective VEGFR2 inhibitor with IC50 of 1 nM. IC50 value: 1 nM Target: VEGFR2 Apatinib, also known as YN968D1, is a tyrosine kinase inhibitor that selectively inhibits the vascular endothelial growth factor
Research Area Cancer
Category Activator
In Vitro YN968D1 slightly inhibits proliferation of HUVEC stimulated by 20% FBS (IC50=23.4 μM), whereas YN968D1 significantly inhibits proliferation stimulated by 20 ng/mL VEGF (IC50=0.17 μM). The IC50 values of Sunitinib are lower under the same conditions (7.4 μM and 0.034 μM, respectively). 1 μM YN968D1 significantly inhibits the migration of HUVEC induced by FBS, but does not affect proliferation of HUVEC, indicating that the inhibitory effect of YN968D1 on FBS-induced migration is not due to the suppression of proliferation. At a concentration of 1 μM, Sunitinib also inhibits the migration of HUVEC.
In Vivo The antitumor potential of YN968D1 is evaluated in six human tumor xenografts in immunodeficient mice. Once-daily oral administration of YN968D1 produces a dose-dependent inhibition of tumor growth in all tumor models examined. Statistically significant growth inhibition is obtained with 50 mg/kg per day YN968D1 in three of five tumor xenografts tested. Each tumor xenograft model is significantly growth inhibited by YN968D1 at the dose of 100 kg/day. Similar tumor growth inhibition is observed (T/C%, 8% to 18%) in mice following treatment with YN968D1 at the dose of 200 kg/day. Full growth inhibition profiles are shown for three of the xenografts. Compared with the control animals, no effect of YN968D1 treatment on bodyweight is observed at any dose level, which suggested that YN968D1 is well tolerated.
Clinical Trial Phase 1; Phase 2; Phase 3; Phase 4
CAS Numbers 1218779-75-9
Pubchem 45139106  
HMDB Not Available
DrugBank Not Available
References
  1. Tian S, Quan H, Xie C, Guo H, Lü F, Xu Y, Li J, Lou L, Yn968d1 Is A Novel And Selective Inhibitor Of Vascular Endothelial Growth Factor Receptor-2 Tyrosine Kinase With Potent Activity In Vitro And In Vivo., Cancer Sci.2011 Jul;102(7):1374-80. Doi: 10.1111/j.1349-7006.2011.01939.x. [PMID:21443688  ]