(Z)-Orantinib ((Z)-SU6668) is a specific, interface-active and ATP-competitive Flk-1/KDR, PDGFRβ and FGFR1 sibling with IC50s of 2.1, 0.008 and 1.2 µM, respectively ( Z)-Olantinib is a potent anti-angiogenic and anti-tumor agent that induces regression of established tumors.

Physicochemical Properties

Molecular Formula	C18H18N2O3
Molecular Weight	310.347
Exact Mass	310.131
CAS #	210644-62-5
Related CAS #	Orantinib;252916-29-3
PubChem CID	5329099
Appearance	Orange to red solid powder
Density	1.3±0.1 g/cm3
Boiling Point	590.5±50.0 °C at 760 mmHg
Flash Point	310.9±30.1 °C
Vapour Pressure	0.0±1.7 mmHg at 25°C
Index of Refraction	1.675
LogP	2.49
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	4
Heavy Atom Count	23
Complexity	516
Defined Atom Stereocenter Count	0
SMILES	CC1=C(NC(=C1CCC(=O)O)C)/C=C\2/C3=CC=CC=C3NC2=O
InChi Key	NHFDRBXTEDBWCZ-ZROIWOOFSA-N
InChi Code	InChI=1S/C18H18N2O3/c1-10-12(7-8-17(21)22)11(2)19-16(10)9-14-13-5-3-4-6-15(13)20-18(14)23/h3-6,9,19H,7-8H2,1-2H3,(H,20,23)(H,21,22)/b14-9-
Chemical Name	3-[2,4-dimethyl-5-[(Z)-(2-oxo-1H-indol-3-ylidene)methyl]-1H-pyrrol-3-yl]propanoic acid
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Flk-1 trans-phosphorylation (Ki=2.1 μM), FGFR1 trans-phosphorylation (Ki=1.2 μM), and PDGFR autophosphorylation (Ki=0.008 μM) are all inhibited by SU6668 (5–15 minutes) [1]. In HUVEC, the VEGF-stimulated rise in KDR tyrosine phosphorylation is inhibited by SU6668 (0.03-10 μM; 60 minutes) [1]. With an IC50 of 0.34 and 9.6 μM, respectively, SU6668 suppresses VEGF- and FGF-induced HUVEC mitosis in a dose-dependent manner [1].
ln Vivo	SU6668 (4-200 mg/kg/day; orally for 21 days) promotes dose-dependent suppression of A431 tumor growth in athymic mice [1]. SU6668 (75 mg/kg/day; intraperitoneally injected for 22 days) effectively reduces tumor angiogenesis and vascularization in mice [1]. SU6668 (200 mg/kg/day; orally for 11-27 days) induces considerable regression of established big A431 xenografts in athymic mice [1].
Animal Protocol	Animal/Disease Models: Female athymic mice (BALB/c, nu/nu) implanted with A431 tumor cells [1] Doses: 4, 40, 75, 200 mg/kg Route of Administration: Oral daily for 21 days Experimental Results: Induction 97% growth inhibition of A431 tumors at dose 97%. No deaths were observed in any treatment group.
ADME/Pharmacokinetics	Metabolism / Metabolites TSU-68 has known human metabolites that include TSU-68 metabolite 1, TSU-68 metabolite 2, and TSU-68 metabolite 3.
References	[1]. SU6668 is a potent antiangiogenic and antitumor agent that induces regression of established tumors. Cancer Res. 2000 Aug 1;60(15):4152-60. [2]. SU6668 inhibits Flk-1/KDR and PDGFRbeta in vivo, resulting in rapid apoptosis of tumor vasculature and tumor regression in mice. FASEB J. 2002 May;16(7):681-90.
Additional Infomation	Orantinib has been used in trials studying the treatment of Lung Cancer, Breast Cancer, Kidney Cancer, Gastric Cancer, and Prostate Cancer, among others. Orantinib is an orally bioavailable receptor tyrosine kinase inhibitor. SU6668 binds to and inhibits the autophosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR), thereby inhibiting angiogenesis and cell proliferation. SU6668 also inhibits the phosphorylation of the stem cell factor receptor tyrosine kinase c-kit, often expressed in acute myelogenous leukemia cells. (NCI04)

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~161.11 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.08 mg/mL (6.70 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.08 mg/mL (6.70 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.2222 mL	16.1108 mL	32.2217 mL
	5 mM	0.6444 mL	3.2222 mL	6.4443 mL
	10 mM	0.3222 mL	1.6111 mL	3.2222 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.