Vatalanib

Summary

Vatalanib (CHEMBL101253) is a phase-3 clinical-stage small-molecule antineoplastic agent targeting PDGFRB, FLT1, and KDR; indicated across 30 conditions including colonic neoplasm and rectal cancer; with CIViC clinical evidence for 2 variant-indication associations (e.g. CSF1R Expression in glioblastoma).

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 4 (PDGFRB, FLT1, KDR…)
• Indications: 30 conditions
• Clinical trials: 35
• Precision-oncology evidence (CIViC): 2 variant–indication associations
• Chemistry: 346.8 Da · C20H15ClN4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL101253
Name	Vatalanib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	151194
ChEBI	CHEBI:90620
Molecular formula	C20H15ClN4
Molecular weight	346.8
InChIKey	YCOYDOIWSSHVCK-UHFFFAOYSA-N

SMILES: C1=CC=C2C(=C1)C(=NN=C2NC3=CC=C(C=C3)Cl)CC4=CC=NC=C4

IUPAC name: N-(4-chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine

ChEBI definition: A member of the class of phthalazines that is phthalazine in which the hydrogens at positions 1 and 4have been replaced by a p-chlorophenylamino group and a pyridin-4-ylmethyl group, respectively. It is a multi-targeted tyrosine kinase inhibitor for all isoforms of VEGFR, PDGFR and c-Kit.

Pharmacological roles (ChEBI): antineoplastic agent, EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor, angiogenesis inhibitor, vascular endothelial growth factor receptor antagonist.

Also known as: CGP-79787, K-222584, NVP-PTK787, Ptk-787, PTK787, Vatalanib, Vatalanib succinate, ZK-222584, ZK222584, PTK-787, vatalanib, SID104171421

Parent form; salt/anhydrous children: CHEMBL75232, CHEMBL2142861

Patent coverage: 3,919 distinct patent families (11,319 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 7,256 (64%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
PDGFRB	platelet derived growth factor receptor beta	Inhibition	6.22	2.3%	P09619
FLT1	fms related receptor tyrosine kinase 1	Inhibition	6.85	0.1%	P17948
KDR	kinase insert domain receptor	Inhibition	7.21	1.1%	P35968
FLT4	fms related receptor tyrosine kinase 4	Inhibition	6.71	0.2%	P35916

Broader ChEMBL bioactivity targets: 21 (assay-derived). Sample: Macrophage colony-stimulating factor 1 receptor, Vascular endothelial growth factor receptor 1, Platelet-derived growth factor receptor beta, Mast/stem cell growth factor receptor Kit, Vascular endothelial growth factor receptor 3, Platelet-derived growth factor receptor alpha, Epidermal growth factor receptor, Proto-oncogene tyrosine-protein kinase receptor Ret, Vascular endothelial growth factor receptor, HLA class I histocompatibility antigen, A alpha chain.

Bioactivity

ChEMBL activities: 106 potent at pChembl ≥ 5 of 107 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
KIT	8.29	Kd	5.1	nM	CHEMBL_ACT_2895947
KIT	8.29	Kd	5.1	nM	CHEMBL_ACT_6220461
KIT	8.29	Kd	5.1	nM	CHEMBL_ACT_7580395
FLT1	8.02	Kd	9.6	nM	CHEMBL_ACT_2907365
FLT1	8.02	Kd	9.6	nM	CHEMBL_ACT_7580463
KDR	8	IC50	10	nM	CHEMBL_ACT_13418836
KDR	7.9	Ki	12.59	nM	CHEMBL_ACT_9577165
KDR	7.8	IC50	16	nM	CHEMBL_ACT_2289037
KDR	7.8	IC50	16	nM	CHEMBL_ACT_2603014
KIT	7.77	Kd	17	nM	CHEMBL_ACT_2897047
KIT	7.77	Kd	17	nM	CHEMBL_ACT_7580400
CSF1R	7.75	Kd	18	nM	CHEMBL_ACT_2902396
KDR	7.7	IC50	20	nM	CHEMBL_ACT_14975687
KDR	7.68	IC50	21	nM	CHEMBL_ACT_1677626
KDR	7.68	IC50	21	nM	CHEMBL_ACT_1694650
KDR	7.68	IC50	21	nM	CHEMBL_ACT_1708939
KDR	7.68	IC50	21	nM	CHEMBL_ACT_2018038
KDR	7.68	IC50	21	nM	CHEMBL_ACT_2288953
KDR	7.68	IC50	21	nM	CHEMBL_ACT_2602426
PDGFRB	7.6	Kd	25	nM	CHEMBL_ACT_2899089
PDGFRB	7.6	Kd	25	nM	CHEMBL_ACT_7580485
KDR	7.43	IC50	37	nM	CHEMBL_ACT_1070524
KDR	7.43	IC50	37	nM	CHEMBL_ACT_3595760
KIT	7.4	Ki	39.81	nM	CHEMBL_ACT_9574930
KDR	7.38	IC50	42	nM	CHEMBL_ACT_2289035
KDR	7.38	IC50	42	nM	CHEMBL_ACT_2603012
KDR	7.38	IC50	42	nM	CHEMBL_ACT_3418610
KDR	7.37	IC50	43	nM	CHEMBL_ACT_12138547
KDR	7.37	IC50	43	nM	CHEMBL_ACT_16434321
KDR	7.37	IC50	43	nM	CHEMBL_ACT_16524726

Target pathways

Aggregated over 4 target gene(s): PDGFRB, FLT1, KDR, FLT4.

Top Reactome pathways

14 total, by targets touching each:

Pathway	Targets	Genes
VEGF binds to VEGFR leading to receptor dimerization	3	FLT1, FLT4, KDR
Neuropilin interactions with VEGF and VEGFR	2	FLT1, KDR
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	2	FLT4, KDR
PIP3 activates AKT signaling	1	PDGFRB
Downstream signal transduction	1	PDGFRB
Signaling by PDGF	1	PDGFRB
Integrin cell surface interactions	1	KDR
Constitutive Signaling by Aberrant PI3K in Cancer	1	PDGFRB
VEGFA-VEGFR2 Pathway	1	KDR
VEGFR2 mediated cell proliferation	1	KDR
RAF/MAP kinase cascade	1	PDGFRB
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	PDGFRB
NOTCH4 Intracellular Domain Regulates Transcription	1	FLT4
Signaling by membrane-tethered fusions of PDGFRA or PDGFRB	1	KDR

Dominant GO biological processes

GO term	Targets
angiogenesis	4
cell surface receptor protein tyrosine kinase signaling pathway	4
positive regulation of cell population proliferation	4
peptidyl-tyrosine phosphorylation	4
positive regulation of cell migration	4
protein autophosphorylation	4
protein phosphorylation	4
cell migration	4
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	3
positive regulation of ERK1 and ERK2 cascade	3
cellular response to vascular endothelial growth factor stimulus	3
positive regulation of MAPK cascade	3
vascular endothelial growth factor receptor signaling pathway	3
vascular endothelial growth factor signaling pathway	3
positive regulation of MAP kinase activity	2

Indications & clinical

Indications

30 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
colonic neoplasm	3	MONDO:0005401	EFO:0004288
rectal cancer	3	MONDO:0006519	EFO:1000657
sarcoma	2	MONDO:0005089	EFO:0000691
diffuse large B-cell lymphoma	2	MONDO:0018905	EFO:0000403
melanoma	2	MONDO:0005105	EFO:0000756
plasma cell myeloma	2	MONDO:0009693	EFO:0001378
neoplasm	2	MONDO:0005070	EFO:0000616
non-small cell lung carcinoma	2	MONDO:0005233	EFO:0003060
mesothelioma	2	MONDO:0005065	EFO:0000588
cutaneous melanoma	2	MONDO:0005012	EFO:0000389
breast neoplasm	2	MONDO:0021100	EFO:0003869
neuroendocrine neoplasm	2	MONDO:0019496	EFO:1001901
von Hippel-Lindau disease	2	MONDO:0008667	MONDO:0008667
age-related macular degeneration	1	MONDO:0005150	EFO:0001365
acute myeloid leukemia	1	MONDO:0018874	EFO:0000222
chronic myeloid leukemia	1	MONDO:0011996	EFO:0000339
glioblastoma	1	MONDO:0018177	EFO:0000519
primary myelofibrosis	1	MONDO:0009692	EFO:0002430
exocrine pancreatic carcinoma	1	MONDO:0005192	EFO:0002618
central nervous system neoplasm	1	MONDO:0006130	EFO:1000158
peritoneal neoplasm	1	MONDO:0006901	MONDO:0002087
fallopian tube neoplasm	1	MONDO:0021092	MONDO:0002158
kidney cancer	1	MONDO:0002367	MONDO:0002367
ovarian cancer	1	MONDO:0008170	MONDO:0008170
endometrium neoplasm	1	MONDO:0021251	MONDO:0011962

5 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 35.

Phase distribution

Phase	Trials
PHASE2	15
PHASE1	10
PHASE1/PHASE2	8
PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00056446	PHASE3	COMPLETED	Study of Oxaliplatin/5-FU/Leucovorin Plus Vatalanib Versus Oxaliplatin/5-FU/Leucovorin in Patients With Previously Treated Metastatic Colorectal Cancer
NCT00056459	PHASE3	COMPLETED	Study of Oxaliplatin/5-FU/Leucovorin Plus Vatalanib Versus Oxaliplatin/5-FU/Leucovorin in Patients With Metastatic Colorectal Cancer.
NCT00052013	PHASE2	COMPLETED	Treatment of Von Hippel-Lindau (VHL)-Related Hemangioblastoma With PTK787/ZK 222584
NCT00053885	PHASE2	COMPLETED	PTK787/ZK 222584 in Treating Patients With Unresectable Malignant Mesothelioma
NCT00072475	PHASE2	COMPLETED	Vatalanib in Treating Patients With Primary or Secondary Myelodysplastic Syndromes
NCT00117299	PHASE2	COMPLETED	PTK787/ZK222584 in the Treatment of Metastatic Gastrointestinal Stromal Tumors Resistant to Imatinib
NCT00128700	PHASE1/PHASE2	COMPLETED	Temozolomide and Radiation Therapy With or Without Vatalanib in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
NCT00134355	PHASE2	COMPLETED	Study of PTK787 in the Treatment of Patients With Non-Metastatic Androgen Independent Prostate Cancer
NCT00138632	PHASE1/PHASE2	COMPLETED	Safety and Efficacy of Oral PTK787 in Patients With Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration (AMD)
NCT00160043	PHASE2	COMPLETED	Safety and Efficacy Study of a New Chemotherapy Agent to Treat Non Small Cell Lung Cancer.
NCT00165347	PHASE2	COMPLETED	Protein Tyrosine Kinases (PTK) in Multiple Myeloma
NCT00171587	PHASE1/PHASE2	COMPLETED	Study of the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Effects of Vatalanib in Combination With Capecitabine in Patients With Advanced Cancer
NCT00185588	PHASE1/PHASE2	COMPLETED	Phase 1-2 Vatalanib and Gemcitabine in Advanced Pancreatic Cancer
NCT00216047	PHASE1/PHASE2	TERMINATED	PTK787 + Trastuzumab for HER2 Overexpressing Metastatic Breast Cancer
NCT00226005	PHASE2	COMPLETED	PTK787 in Patients With Advanced Metastatic Pancreatic Adenocarcinoma
NCT00227773	PHASE2	WITHDRAWN	Vatalanib and Octreotide in Treating Patients With Progressive Neuroendocrine Tumors
NCT00240162	PHASE2	TERMINATED	PTK/ZK as Post Transplant Maintenance Therapy in Patients With Multiple Myeloma
NCT00263198	PHASE2	TERMINATED	PTK and Letrozole in Post-menopausal Women With Advanced Breast Cancer
NCT00281125	PHASE1/PHASE2	TERMINATED	Phase I/II Trial of PTK787 and Pemetrexed With or Without Cisplatin for Lung Cancer
NCT00293371	PHASE1/PHASE2	TERMINATED	Docetaxel, Prednisone, and Vatalanib in Treating Patients With Advanced Prostate Cancer
NCT00348790	PHASE2	COMPLETED	Vatalanib in Treating Patients With Recurrent or Progressive Meningioma
NCT00511043	PHASE2	TERMINATED	PTK787 in Refractory or Relapsed Diffuse Large Cell Lymphoma
NCT00563823	PHASE2	COMPLETED	Vatalanib in Treating Patients With Metastatic Cutaneous Melanoma That Cannot be Removed by Surgery
NCT00590343	PHASE2	COMPLETED	Safety and Efficacy Study of PTK787/ZK222584 to Treat Metastatic Neuroendocrine Tumors
NCT00615160	PHASE1/PHASE2	TERMINATED	PTK/ZK in Disseminated Malignant Melanoma
NCT00268918	PHASE1	COMPLETED	Docetaxel and PTK787 in Metastatic Breast Cancer Patients and Gynecological Cancer Patients
NCT00303732	PHASE1	COMPLETED	Vatalanib and Everolimus in Treating Patients With Advanced Solid Tumors
NCT00358163	PHASE1	TERMINATED	Trial of PTK787/ZK 222584 Plus Paclitaxel
NCT00385853	PHASE1	COMPLETED	PTK787/ZK 222584 in Combination With Temozolomide and Radiation in Patients With Glioblastoma Taking Enzyme-Inducing Anti-Epileptic Drugs
NCT00387933	PHASE1	COMPLETED	Imatinib Mesylate, Vatalanib, and Hydroxyurea in Treating Patients With Recurrent or Relapsed Malignant Glioma
NCT00390000	PHASE1	COMPLETED	Vatalanib and Pemetrexed Disodium in Treating Patients With Advanced Solid Tumors
NCT00426452	PHASE1	COMPLETED	A Drug-drug Interaction Study of Oral 1250 mg of Vatalinib Administered Under Fasting and Fed Conditions With a Proton-pump Inhibitor in Healthy Sterile or Postmenopausal Female Volunteers
NCT00611689	PHASE1	COMPLETED	Imatinib and PTK787/ZK222584 in Refractory and/or Advanced Solid Tumors
NCT00611793	PHASE1	COMPLETED	PTK787/ZK222584 With Bevacizumab in Patients With Refractory and/or Advanced Malignancies
NCT00655655	PHASE1	COMPLETED	Everolimus and Vatalanib in Treating Patients With Advanced Solid Tumors

Clinical evidence (CIViC)

Variant × indication × effect (2 predictive associations from 2 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
CSF1R Expression	Glioblastoma	Sensitivity/Response	Vatalanib + Pexidartinib	CIViC D	EID8133
PTPRB Loss-of-function	Angiosarcoma	Sensitivity/Response	Vatalanib + Sunitinib	CIViC D	EID1895

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

198 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
Crizotinib	ChEMBL + PubChem	Phase 4 (approved)	FLT1, FLT4, KDR, PDGFRB
PAZOPANIB	ChEMBL + PubChem	Phase 4 (approved)	FLT1, FLT4, KDR, PDGFRB
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	FLT1, FLT4, KDR, PDGFRB
AXITINIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR, PDGFRB
ERLOTINIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR, PDGFRB
FEDRATINIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR, PDGFRB
LENVATINIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR, PDGFRB
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR, PDGFRB
NINTEDANIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR, PDGFRB
NINTEDANIB ESYLATE	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR, PDGFRB
QUIZARTINIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR, PDGFRB
SORAFENIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR, PDGFRB
SUNITINIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR, PDGFRB
TIVOZANIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR, PDGFRB
VANDETANIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR, PDGFRB
BRIVANIB	ChEMBL	Phase 3	FLT1, FLT4, KDR, PDGFRB
CEDIRANIB	ChEMBL	Phase 3	FLT1, FLT4, KDR, PDGFRB
DOVITINIB	ChEMBL	Phase 3	FLT1, FLT4, KDR, PDGFRB
LESTAURTINIB	ChEMBL	Phase 3	FLT1, FLT4, KDR, PDGFRB
LINIFANIB	ChEMBL	Phase 3	FLT1, FLT4, KDR, PDGFRB
MOTESANIB	ChEMBL	Phase 3	FLT1, FLT4, KDR, PDGFRB
SEMAXANIB	ChEMBL	Phase 3	FLT1, FLT4, KDR, PDGFRB
BFH-772	ChEMBL	Phase 2	FLT1, FLT4, KDR, PDGFRB
CENISERTIB	ChEMBL	Phase 2	FLT1, FLT4, KDR, PDGFRB
DEFOSBARASERTIB	ChEMBL	Phase 2	FLT1, FLT4, KDR, PDGFRB
DORAMAPIMOD	ChEMBL	Phase 2	FLT1, FLT4, KDR, PDGFRB
FORETINIB	ChEMBL	Phase 2	FLT1, FLT4, KDR, PDGFRB
ILORASERTIB	ChEMBL	Phase 2	FLT1, FLT4, KDR, PDGFRB
LUCITANIB	ChEMBL	Phase 2	FLT1, FLT4, KDR, PDGFRB
MK-2461	ChEMBL	Phase 2	FLT1, FLT4, KDR, PDGFRB
OSI-632	ChEMBL	Phase 2	FLT1, FLT4, KDR, PDGFRB
R-406	ChEMBL	Phase 2	FLT1, FLT4, KDR, PDGFRB
RAF-265	ChEMBL	Phase 2	FLT1, FLT4, KDR, PDGFRB
SU-014813	ChEMBL	Phase 2	FLT1, FLT4, KDR, PDGFRB
TANDUTINIB	ChEMBL	Phase 2	FLT1, FLT4, KDR, PDGFRB
TOZASERTIB	ChEMBL	Phase 2	FLT1, FLT4, KDR, PDGFRB
Afatinib	PubChem	Approved	FLT1, FLT4, KDR, PDGFRB
Selumetinib	PubChem	Approved	FLT1, FLT4, KDR, PDGFRB
Gefitinib	ChEMBL + PubChem	Phase 4 (approved)	FLT1, FLT4, KDR
CABOZANTINIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR
DASATINIB	ChEMBL	Phase 4 (approved)	FLT1, KDR, PDGFRB
ENTRECTINIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR
FRUQUINTINIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR
INFIGRATINIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR
PEXIDARTINIB	ChEMBL	Phase 4 (approved)	FLT1, KDR, PDGFRB
PONATINIB	ChEMBL	Phase 4 (approved)	FLT1, KDR, PDGFRB
CANERTINIB	ChEMBL	Phase 3	FLT1, KDR, PDGFRB
CEP-1347	ChEMBL	Phase 3	FLT1, FLT4, KDR
ORANTINIB	ChEMBL	Phase 3	FLT1, KDR, PDGFRB
SURUFATINIB	ChEMBL	Phase 3	FLT1, FLT4, KDR
AEE-788	ChEMBL	Phase 2	FLT1, KDR, PDGFRB
AT-9283	ChEMBL	Phase 2	FLT1, FLT4, KDR
CEP-32496	ChEMBL	Phase 2	FLT1, KDR, PDGFRB
ELLAGIC ACID	ChEMBL	Phase 2	FLT4, KDR, PDGFRB
REBASTINIB	ChEMBL	Phase 2	FLT1, FLT4, KDR
SOTRASTAURIN	ChEMBL	Phase 2	FLT4, KDR, PDGFRB
TELATINIB	ChEMBL	Phase 2	FLT4, KDR, PDGFRB
Idelalisib	PubChem	Approved	FLT1, FLT4, PDGFRB
BRIGATINIB	ChEMBL	Phase 4 (approved)	FLT4, KDR
FILGOTINIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4