Molecule Details
InChIKeyXZXHXSATPCNXJR-ZIADKAODSA-N
Canonical SMILESCOC(=O)c1ccc2c(c1)NC(=O)/C2=C(\Nc1ccc(N(C)C(=O)CN2CCN(C)CC2)cc1)c1ccccc1
Clinical Status Clinical Multi-Target
Targets (Human+Pathogen)165
Pfam Stratification Cross-Family
Avg pChEMBL7.03
SourceChEMBL;BindingDB;TTD_MultiTarget
2D Structure
2D structure
Activity Profile
DrugBank Annotations
DrugBank ID DB09079
Drug NameNintedanib
CAS Number656247-17-5
Groups approved investigational
ATC Codes L01EX09
DescriptionNintedanib is a small molecule kinase inhibitor used in the treatment of pulmonary fibrosis, systemic sclerosis-associated interstitial lung disease, and non-small cell lung cancer (NSCLC).[L8453,L8459] It was first approved for use in the United States in 2014.[L8453] Within the spectrum of idiopat...

Categories: Antifibrotic Agents Antineoplastic Agents Antineoplastic and Immunomodulating Agents Cytochrome P-450 CYP3A Substrates Cytochrome P-450 CYP3A4 Substrates Cytochrome P-450 CYP3A4 Substrates (strength unknown) Cytochrome P-450 Substrates Enzyme Inhibitors Heterocyclic Compounds, Fused-Ring Kinase Inhibitor OCT1 inhibitors OCT1 substrates P-glycoprotein inhibitors P-glycoprotein substrates Protein Kinase Inhibitors Tyrosine Kinase Inhibitors UGT1A1 Substrates
Cross-references: BindingDB: 50026612 ChEBI: 85164 CHEMBL502835 ChemSpider: 7985471 Drugs Product Database (DPD): 22614 D10481 PDB: XIN PubChem:9809715 PubChem:310265007 RxCUI: 1592737 Wikipedia: Nintedanib ZINC: ZINC000100014909
Target Activities (165)
Target Gene Organism Category Pfam pChEMBL Type Source
Q13163 MAP2K5 Homo sapiens Human PF00564 PF00069 8.7 Kd ChEMBL;BindingDB
Q9NSY1 BMP2K Homo sapiens Human PF15282 PF00069 8.7 Kd ChEMBL;BindingDB
Q12809 KCNH2 Homo sapiens Human PF00027 PF00520 PF13426 8.6 IC50 ChEMBL;BindingDB
P36888 FLT3 Homo sapiens Human PF00047 PF07714 8.4 Kd ChEMBL;BindingDB
O43318 MAP3K7 Homo sapiens Human PF07714 8.4 Kd ChEMBL;BindingDB
P04629 NTRK1 Homo sapiens Human PF13855 PF16920 PF07714 PF18613 8.3 Kd ChEMBL;BindingDB
P35968 KDR Homo sapiens Human PF07679 PF00047 PF13895 PF22971 PF07714 PF21339 PF17988 PF22854 8.3 IC50 ChEMBL;BindingDB
P23458 JAK1 Homo sapiens Human PF18379 PF18377 PF17887 PF07714 PF21990 8.3 Kd ChEMBL;BindingDB
Q56UN5 MAP3K19 Homo sapiens Human PF00069 8.3 Kd ChEMBL;BindingDB
P09619 PDGFRB Homo sapiens Human PF00047 PF13927 PF25305 PF07714 8.1 IC50 ChEMBL;BindingDB
P52333 JAK3 Homo sapiens Human PF18379 PF18377 PF17887 PF07714 PF21990 8.1 Kd ChEMBL;BindingDB
P16234 PDGFRA Homo sapiens Human PF07679 PF25305 PF07714 8.1 IC50 ChEMBL;BindingDB
Q13523 PRP4K Homo sapiens Human PF00069 8.1 Kd ChEMBL;BindingDB
Q12866 MERTK Homo sapiens Human PF00041 PF00047 PF13927 PF07714 8.1 Kd ChEMBL;BindingDB
P49759 CLK1 Homo sapiens Human PF00069 8.1 Kd ChEMBL;BindingDB
Q13043 STK4 Homo sapiens Human PF11629 PF00069 8.1 Kd ChEMBL;BindingDB
Q9Y2U5 MAP3K2 Homo sapiens Human PF00564 PF00069 8.0 Kd ChEMBL;BindingDB
Q02750 MAP2K1 Homo sapiens Human PF00069 8.0 Kd ChEMBL;BindingDB
P30530 AXL Homo sapiens Human PF00041 PF13927 PF07714 7.9 Kd ChEMBL;BindingDB
Q08345 DDR1 Homo sapiens Human PF21114 PF00754 PF07714 7.9 Kd ChEMBL;BindingDB
Q9UPE1 SRPK3 Homo sapiens Human PF00069 7.9 Kd ChEMBL;BindingDB
P35916 FLT4 Homo sapiens Human PF07679 PF13927 PF22971 PF07714 PF21339 PF17988 PF22854 7.9 IC50 ChEMBL;BindingDB
P10721 KIT Homo sapiens Human PF00047 PF07714 7.9 Kd ChEMBL;BindingDB
O60674 JAK2 Homo sapiens Human PF18379 PF18377 PF17887 PF07714 PF21990 7.8 Kd ChEMBL;BindingDB
Q13976 PRKG1 Homo sapiens Human PF00027 PF16808 PF00069 7.8 Kd ChEMBL;BindingDB
P06239 LCK Homo sapiens Human PF07714 PF00017 PF00018 7.8 IC50 ChEMBL;BindingDB
P32298 GRK4 Homo sapiens Human PF00069 PF00615 7.8 Kd ChEMBL;BindingDB
P78356 PIP4K2B Homo sapiens Human PF01504 7.8 Kd ChEMBL;BindingDB
P07949 RET Homo sapiens Human PF00028 PF07714 PF17756 PF17812 PF17813 PF22540 7.8 Kd ChEMBL;BindingDB
O75716 STK16 Homo sapiens Human PF00069 7.7 Kd ChEMBL;BindingDB
Q15831 STK11 Homo sapiens Human PF00069 7.7 Kd ChEMBL;BindingDB
Q9HAZ1 CLK4 Homo sapiens Human PF00069 7.7 Kd ChEMBL;BindingDB
Q16620 NTRK2 Homo sapiens Human PF07679 PF13855 PF16920 PF01462 PF07714 7.7 Kd ChEMBL;BindingDB
P14616 INSRR Homo sapiens Human PF00041 PF00757 PF07714 PF01030 7.7 Kd ChEMBL;BindingDB
Q00536 CDK16 Homo sapiens Human PF00069 7.7 Kd ChEMBL;BindingDB
Q9H093 NUAK2 Homo sapiens Human PF00069 7.7 Kd ChEMBL;BindingDB
P33981 TTK Homo sapiens Human PF00069 7.7 Kd ChEMBL;BindingDB
Q9BRS2 RIOK1 Homo sapiens Human PF01163 7.6 Kd ChEMBL;BindingDB
P06213 INSR Homo sapiens Human PF00757 PF17870 PF07714 PF01030 7.6 Kd ChEMBL;BindingDB
Q02161 RHD Homo sapiens Human PF00909 7.6 pIC50 TTD_MultiTarget
Q9UM73 ALK Homo sapiens Human PF12810 PF00629 PF07714 7.5 Kd ChEMBL;BindingDB
Q16288 NTRK3 Homo sapiens Human PF07679 PF00047 PF13855 PF16920 PF01462 PF07714 7.5 Kd ChEMBL;BindingDB
P11362 FGFR1 Homo sapiens Human PF07679 PF00047 PF07714 7.5 pIC50 TTD_MultiTarget
P17948 FLT1 Homo sapiens Human PF07679 PF00047 PF13927 PF22971 PF07714 PF21339 PF17988 PF22854 7.5 IC50 ChEMBL;BindingDB
Q99759 MAP3K3 Homo sapiens Human PF00564 PF00069 7.5 Kd ChEMBL;BindingDB
Q92918 MAP4K1 Homo sapiens Human PF00780 PF00069 7.5 Kd ChEMBL;BindingDB
O14730 RIOK3 Homo sapiens Human PF01163 7.4 Kd ChEMBL;BindingDB
P78362 SRPK2 Homo sapiens Human PF00069 7.4 Kd ChEMBL;BindingDB
P21802 FGFR2 Homo sapiens Human PF07679 PF13927 PF07714 7.4 IC50 ChEMBL;BindingDB
Q96SB4 SRPK1 Homo sapiens Human PF00069 7.4 Kd ChEMBL;BindingDB
Q13188 STK3 Homo sapiens Human PF11629 PF00069 7.4 Kd ChEMBL;BindingDB
P36507 MAP2K2 Homo sapiens Human PF00069 7.4 Kd ChEMBL;BindingDB
Q16832 DDR2 Homo sapiens Human PF21114 PF00754 PF07714 7.4 Kd ChEMBL;BindingDB
Q5S007 LRRK2 Homo sapiens Human PF23745 PF23744 PF23748 PF16095 PF25497 PF13855 PF00069 PF08477 7.4 Kd ChEMBL;BindingDB
Q14680 MELK Homo sapiens Human PF02149 PF00069 PF21594 7.4 IC50 ChEMBL;BindingDB
P07333 CSF1R Homo sapiens Human PF00047 PF25305 PF07714 7.3 Kd ChEMBL;BindingDB
Q99755 PIP5K1A Homo sapiens Human PF01504 7.3 Kd ChEMBL;BindingDB
Q9P289 STK26 Homo sapiens Human PF20929 PF00069 7.3 Kd ChEMBL;BindingDB
Q9H2G2 SLK Homo sapiens Human PF00069 PF12474 7.3 Kd ChEMBL;BindingDB
O00444 PLK4 Homo sapiens Human PF00069 PF18190 PF18409 7.3 Kd ChEMBL;BindingDB
Q9UKE5 TNIK Homo sapiens Human PF00780 PF00069 7.3 Kd ChEMBL;BindingDB
Q13873 BMPR2 Homo sapiens Human PF01064 PF00069 7.2 Kd ChEMBL;BindingDB
Q15349 RPS6KA2 Homo sapiens Human PF00069 PF00433 7.2 Kd ChEMBL;BindingDB
Q6PHR2 ULK3 Homo sapiens Human PF04212 PF00069 7.2 Kd ChEMBL;BindingDB
P08069 IGF1R Homo sapiens Human PF00757 PF07714 PF01030 7.2 Kd ChEMBL;BindingDB
P00519 ABL1 Homo sapiens Human PF08919 PF07714 PF00017 PF00018 7.2 Kd ChEMBL;BindingDB
Q2M2I8 AAK1 Homo sapiens Human PF00069 7.2 Kd ChEMBL;BindingDB
P51812 RPS6KA3 Homo sapiens Human PF00069 PF00433 7.2 Kd ChEMBL;BindingDB
P16591 FER Homo sapiens Human PF00611 PF07714 PF00017 7.1 Kd ChEMBL;BindingDB
P07947 YES1 Homo sapiens Human PF07714 PF00017 PF00018 7.1 Kd ChEMBL;BindingDB
Q14289 PTK2B Homo sapiens Human PF21477 PF00373 PF18038 PF03623 PF07714 7.1 Kd ChEMBL;BindingDB
Q8N4C8 MINK1 Homo sapiens Human PF00780 PF00069 7.1 Kd ChEMBL;BindingDB
P49841 GSK3B Homo sapiens Human PF00069 7.1 Kd ChEMBL;BindingDB
P54646 PRKAA2 Homo sapiens Human PF16579 PF21147 PF00069 7.1 Kd ChEMBL;BindingDB
O94804 STK10 Homo sapiens Human PF00069 PF12474 7.1 Kd ChEMBL;BindingDB
Q13131 PRKAA1 Homo sapiens Human PF16579 PF21147 PF00069 7.1 Kd ChEMBL;BindingDB
Q00537 CDK17 Homo sapiens Human PF00069 7.0 Kd ChEMBL;BindingDB
P22607 FGFR3 Homo sapiens Human PF21165 PF07679 PF13927 PF07714 7.0 IC50 ChEMBL;BindingDB
Q32MK0 MYLK3 Homo sapiens Human PF00069 7.0 Kd ChEMBL;BindingDB
Q52WX2 SBK1 Homo sapiens Human PF00069 7.0 Kd ChEMBL;BindingDB
Q9UEE5 STK17A Homo sapiens Human PF00069 7.0 Kd ChEMBL;BindingDB
Q9Y6E0 STK24 Homo sapiens Human PF20929 PF00069 7.0 Kd ChEMBL;BindingDB
P51617 IRAK1 Homo sapiens Human PF00531 PF00069 6.9 Kd ChEMBL;BindingDB
P29597 TYK2 Homo sapiens Human PF18379 PF18377 PF17887 PF07714 PF21990 6.9 Kd ChEMBL;BindingDB
O15197 EPHB6 Homo sapiens Human PF14575 PF25599 PF01404 PF07699 PF00041 PF07714 PF07647 6.8 Kd ChEMBL;BindingDB
O43283 MAP3K13 Homo sapiens Human PF07714 6.8 Kd ChEMBL;BindingDB
Q12852 MAP3K12 Homo sapiens Human PF07714 6.8 Kd ChEMBL;BindingDB
Q16816 PHKG1 Homo sapiens Human PF00069 6.8 Kd ChEMBL;BindingDB
Q00526 CDK3 Homo sapiens Human PF00069 6.8 Kd ChEMBL
O95819 MAP4K4 Homo sapiens Human PF00780 PF00069 6.8 Kd ChEMBL;BindingDB
P29376 LTK Homo sapiens Human PF12810 PF07714 6.8 Kd ChEMBL;BindingDB
Q9UHD2 TBK1 Homo sapiens Human PF00069 PF18394 PF18396 6.8 Kd ChEMBL;BindingDB
P12931 SRC Homo sapiens Human PF07714 PF00017 PF00018 6.8 IC50 ChEMBL;BindingDB
O60285 NUAK1 Homo sapiens Human PF00069 6.8 Kd ChEMBL;BindingDB
Q14164 IKBKE Homo sapiens Human PF00069 PF18394 PF18396 6.8 Kd ChEMBL;BindingDB
Q15418 RPS6KA1 Homo sapiens Human PF00069 PF00433 6.7 Kd ChEMBL;BindingDB
P23443 RPS6KB1 Homo sapiens Human PF00069 PF00433 6.7 Kd ChEMBL;BindingDB
Q9UQB9 AURKC Homo sapiens Human PF00069 6.7 Kd ChEMBL;BindingDB
P07948 LYN Homo sapiens Human PF07714 PF00017 PF00018 6.7 IC50 ChEMBL;BindingDB
O75582 RPS6KA5 Homo sapiens Human PF00069 PF00433 6.7 Kd ChEMBL;BindingDB
O75914 PAK3 Homo sapiens Human PF00786 PF00069 6.7 Kd ChEMBL;BindingDB
Q05397 PTK2 Homo sapiens Human PF21477 PF00373 PF18038 PF03623 PF07714 6.7 Kd ChEMBL;BindingDB
Q08881 ITK Homo sapiens Human PF00779 PF00169 PF07714 PF00017 PF00018 6.7 Kd ChEMBL;BindingDB
Q13470 TNK1 Homo sapiens Human PF07714 PF22931 6.7 Kd ChEMBL;BindingDB
P80192 MAP3K9 Homo sapiens Human PF07714 PF14604 6.7 Kd ChEMBL;BindingDB
P49674 CSNK1E Homo sapiens Human PF00069 6.6 Kd ChEMBL;BindingDB
Q9UK32 RPS6KA6 Homo sapiens Human PF00069 PF00433 6.6 Kd ChEMBL;BindingDB
Q13546 RIPK1 Homo sapiens Human PF00531 PF07714 6.6 Kd ChEMBL;BindingDB
P15735 PHKG2 Homo sapiens Human PF00069 6.6 Kd ChEMBL;BindingDB
Q96NX5 CAMK1G Homo sapiens Human PF00069 6.6 Kd ChEMBL;BindingDB
P53779 MAPK10 Homo sapiens Human PF00069 6.6 Kd ChEMBL;BindingDB
Q9H0K1 SIK2 Homo sapiens Human PF00069 PF23312 6.5 Kd ChEMBL;BindingDB
O14757 CHEK1 Homo sapiens Human PF00069 6.5 Kd ChEMBL;BindingDB
Q12851 MAP4K2 Homo sapiens Human PF00780 PF00069 6.5 Kd ChEMBL;BindingDB
Q15746 MYLK Homo sapiens Human PF16620 PF00041 PF07679 PF00069 6.5 Kd ChEMBL;BindingDB
Q8IVH8 MAP4K3 Homo sapiens Human PF00780 PF00069 6.5 Kd ChEMBL;BindingDB
P09769 FGR Homo sapiens Human PF07714 PF00017 PF00018 6.5 Kd ChEMBL;BindingDB
P11274 BCR Homo sapiens Human PF09036 PF00168 PF19057 PF00620 PF00621 6.5 Kd ChEMBL
P50613 CDK7 Homo sapiens Human PF00069 6.5 Kd ChEMBL;BindingDB
Q06187 BTK Homo sapiens Human PF00779 PF00169 PF07714 PF00017 PF00018 6.5 Kd ChEMBL;BindingDB
O75385 ULK1 Homo sapiens Human PF12063 PF21127 PF00069 6.5 Kd ChEMBL;BindingDB
P08581 MET Homo sapiens Human PF07714 PF01437 PF01403 PF01833 6.5 Kd ChEMBL;BindingDB
P11802 CDK4 Homo sapiens Human PF00069 6.5 Kd ChEMBL;BindingDB
P51451 BLK Homo sapiens Human PF07714 PF00017 PF00018 6.4 Kd ChEMBL;BindingDB
Q8IYT8 ULK2 Homo sapiens Human PF12063 PF21127 PF00069 6.4 Kd ChEMBL;BindingDB
Q9NRM7 LATS2 Homo sapiens Human PF00069 PF00433 6.4 Kd ChEMBL;BindingDB
Q9Y4K4 MAP4K5 Homo sapiens Human PF00780 PF00069 6.4 Kd ChEMBL;BindingDB
O95835 LATS1 Homo sapiens Human PF00069 PF00433 PF00627 6.4 Kd ChEMBL;BindingDB
Q96GD4 AURKB Homo sapiens Human PF00069 6.4 Kd ChEMBL;BindingDB
P49840 GSK3A Homo sapiens Human PF00069 6.4 Kd ChEMBL;BindingDB
P57078 RIPK4 Homo sapiens Human PF12796 PF13637 PF00069 6.4 Kd ChEMBL;BindingDB
Q86YV6 MYLK4 Homo sapiens Human PF00069 6.4 Kd ChEMBL;BindingDB
O94921 CDK14 Homo sapiens Human PF00069 6.3 Kd ChEMBL;BindingDB
Q07002 CDK18 Homo sapiens Human PF00069 6.3 Kd ChEMBL;BindingDB
Q9UEW8 STK39 Homo sapiens Human PF12202 PF00069 6.3 Kd ChEMBL;BindingDB
O15075 DCLK1 Homo sapiens Human PF03607 PF00069 6.3 Kd ChEMBL;BindingDB
P54762 EPHB1 Homo sapiens Human PF14575 PF25599 PF01404 PF00041 PF07714 PF00536 6.3 Kd ChEMBL;BindingDB
O15146 MUSK Homo sapiens Human PF01392 PF07679 PF13927 PF07714 6.2 Kd ChEMBL;BindingDB
Q04771 ACVR1 Homo sapiens Human PF01064 PF07714 PF08515 6.2 Kd ChEMBL;BindingDB
O75676 RPS6KA4 Homo sapiens Human PF00069 PF00433 6.2 Kd ChEMBL;BindingDB
P22455 FGFR4 Homo sapiens Human PF07679 PF13927 PF07714 6.2 IC50 ChEMBL;BindingDB
P06241 FYN Homo sapiens Human PF07714 PF00017 PF00018 6.2 Kd ChEMBL;BindingDB
P45983 MAPK8 Homo sapiens Human PF00069 6.2 Kd ChEMBL;BindingDB
Q8N5S9 CAMKK1 Homo sapiens Human PF00069 6.2 Kd ChEMBL;BindingDB
O94806 PRKD3 Homo sapiens Human PF00130 PF00169 PF00069 PF25525 6.2 Kd ChEMBL;BindingDB
O94768 STK17B Homo sapiens Human PF00069 6.2 Kd ChEMBL;BindingDB
P57059 SIK1 Homo sapiens Human PF00069 PF23312 6.2 Kd ChEMBL;BindingDB
Q16584 MAP3K11 Homo sapiens Human PF07714 PF14604 6.2 Kd ChEMBL;BindingDB
Q9BZL6 PRKD2 Homo sapiens Human PF00130 PF00169 PF00069 PF25525 6.1 Kd ChEMBL;BindingDB
Q16512 PKN1 Homo sapiens Human PF02185 PF00069 PF00433 6.1 Kd ChEMBL;BindingDB
P49760 CLK2 Homo sapiens Human PF00069 6.1 Kd ChEMBL;BindingDB
P27448 MARK3 Homo sapiens Human PF02149 PF00069 PF00627 6.1 Kd ChEMBL;BindingDB
Q9C098 DCLK3 Homo sapiens Human PF00069 6.1 Kd ChEMBL;BindingDB
Q9H2X6 HIPK2 Homo sapiens Human PF00069 6.1 Kd ChEMBL;BindingDB
Q8TDR2 STK35 Homo sapiens Human PF00069 6.1 Kd ChEMBL;BindingDB
Q9NWZ3 IRAK4 Homo sapiens Human PF07714 6.1 Kd ChEMBL;BindingDB
P42681 TXK Homo sapiens Human PF07714 PF00017 PF00018 6.1 Kd ChEMBL;BindingDB
Q9H422 HIPK3 Homo sapiens Human PF00069 6.1 Kd ChEMBL;BindingDB
P19784 CSNK2A2 Homo sapiens Human PF00069 6.0 Kd ChEMBL;BindingDB
Q96RR4 CAMKK2 Homo sapiens Human PF00069 6.0 Kd ChEMBL;BindingDB
Q9UF33 EPHA6 Homo sapiens Human PF14575 PF25599 PF01404 PF07699 PF00041 PF07714 PF00536 6.0 Kd ChEMBL;BindingDB
Q15139 PRKD1 Homo sapiens Human PF00130 PF00169 PF00069 PF25525 6.0 Kd ChEMBL;BindingDB
Q15835 GRK1 Homo sapiens Human PF00069 PF00615 6.0 Kd ChEMBL;BindingDB
Q96BR1 SGK3 Homo sapiens Human PF00069 PF00433 PF00787 6.0 Kd ChEMBL;BindingDB
P9WI81 pknB Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) Pathogen PF03793 PF00069 8.4 Kd ChEMBL;BindingDB
DrugBank Target Actions (23)
Target Gene Target Name Action Type
P02768 ALB Albumin substrate carriers
P08684 CYP3A4 Cytochrome P450 3A4 substrate enzymes
P22309 UGT1A1 UDP-glucuronosyltransferase 1A1 substrate enzymes
Q9HAW7 Q9HAW7 UDP-glucuronosyltransferase 1A7 substrate enzymes
Q9HAW8 Q9HAW8 UDP-glucuronosyltransferase 1A10 substrate enzymes
Q9HAW9 Q9HAW9 UDP-glucuronosyltransferase 1A8 substrate enzymes
P06239 LCK Tyrosine-protein kinase Lck inhibitor targets
P07948 LYN Tyrosine-protein kinase Lyn inhibitor targets
P09619 PDGFRB Platelet-derived growth factor receptor beta inhibitor targets
P11362 FGFR1 Fibroblast growth factor receptor 1 inhibitor targets
P12931 SRC Proto-oncogene tyrosine-protein kinase Src inhibitor targets
P16234 PDGFRA Platelet-derived growth factor receptor alpha inhibitor targets
P17948 FLT1 Vascular endothelial growth factor receptor 1 inhibitor targets
P21802 FGFR2 Fibroblast growth factor receptor 2 inhibitor targets
P22607 FGFR3 Fibroblast growth factor receptor 3 inhibitor targets
P35916 FLT4 Vascular endothelial growth factor receptor 3 inhibitor targets
P35968 KDR Vascular endothelial growth factor receptor 2 inhibitor targets
P36888 FLT3 Receptor-type tyrosine-protein kinase FLT3 inhibitor targets
Q9UNQ0 ABCG2 Broad substrate specificity ATP-binding cassette transporter ABCG2 binder transporters
O15245 SLC22A1 Solute carrier family 22 member 1 inhibitor transporters
P08183 ABCB1 ATP-dependent translocase ABCB1 inhibitor transporters
O15245 SLC22A1 Solute carrier family 22 member 1 substrate transporters
P08183 ABCB1 ATP-dependent translocase ABCB1 substrate transporters