SKLB1002(SKLB-1002 SKLB 1002)

Molecular Weight (MW)	320.39
Formula	C13H12N4O2S2
CAS No.	1225451-84-2
Storage	-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)	DMSO: 7 mg/mL (21.8 mM)
Water:<1 mg/mL
Ethanol: <1 mg/mL
SMILES	CC1=NN=C(SC2=C3C=C(OC)C(OC)=CC3=NC=N2)S1
Synonyms	SKLB 1002; SKLB1002; SKLB-1002; 2-((6,7-dimethoxyquinazolin-4-yl)thio)-5-methyl-1,3,4-thiadiazole InChi Key: RQVGFDBMONQTBC-UHFFFAOYSA-N InChi Code: InChI=1S/C13H12N4O2S2/c1-7-16-17-13(20-7)21-12-8-4-10(18-2)11(19-3)5-9(8)14-6-15-12/h4-6H,1-3H3 SMILES Code: CC1=NN=C(SC2=C3C=C(OC)C(OC)=CC3=NC=N2)S1

Molecular Weight (MW)

320.39

Formula

C13H12N4O2S2

CAS No.

1225451-84-2

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 7 mg/mL (21.8 mM)

Water:<1 mg/mL

Ethanol: <1 mg/mL

SMILES

CC1=NN=C(SC2=C3C=C(OC)C(OC)=CC3=NC=N2)S1

Synonyms

SKLB 1002; SKLB1002; SKLB-1002; 2-((6,7-dimethoxyquinazolin-4-yl)thio)-5-methyl-1,3,4-thiadiazole

InChi Key: RQVGFDBMONQTBC-UHFFFAOYSA-N

InChi Code: InChI=1S/C13H12N4O2S2/c1-7-16-17-13(20-7)21-12-8-4-10(18-2)11(19-3)5-9(8)14-6-15-12/h4-6H,1-3H3

SMILES Code: CC1=NN=C(SC2=C3C=C(OC)C(OC)=CC3=NC=N2)S1

In Vitro	In vitro activity: SKLB1002 shows strikingly lower cytotoxicity on normal human cells L-02. SKLB1002 significantly inhibits HUVEC proliferation, migration, invasion, and tube formation, by inhibiting VEGF-induced phosphorylation of VEGFR2 kinase and the downstream protein kinases including ERK, FAK, and Src. Kinase Assay: Kinase inhibition is measured by the use of radiometric assays conducted by Kinase Profiler service. Briefly, in the presence or absence of SKLB1002, VGFR2 (5–10 mU) is incubated in 25-μL reaction solution containing 8 mmol/L 3-(N-morpholino)propanesulfonic acid (MOPS), pH 7.0, 0.2 mmol/L EDTA, 0.33 mg/mL myelin basic protein, 10 mmol/L Mg acetate, and γ-[33P]ATP. After incubation for 40 minutes at room temperature, the reaction is stopped and 10 μL of the reaction solution is then spotted onto a P30 filtermat and washed 3 times for 5 minutes in 75 mmol/L phosphoric acid and once in methanol prior to scintillation counting. Cell Assay: Cell proliferation is measured using MTT assay. Various cells including HUVECs, L-02, B16-F10, HepG2, and SW620 are treated with indicated concentrations of SKLB1002 for 24 hours. Vandetanib and sunitinib serve as positive controls. Each assay is replicated 3 times.
In Vivo	In the zebrafish embryos, SKLB1002 remarkably blocks the formation of embryonic and tumor-induced angiogenesis with no or least impact on normal cell proliferation. In athymic mice bearing SW620 or HepG2 xenografts, SKLB1002 (100 mg/kg daily, i.p.) causes significant inhibition of tumor growth, inhibits tumor angiogenesis and induces tumor apoptosis. In 4T1 and CT26 tumor model, SKLB1002 and local hyperthermia produce a synergistic antiangiogenesis, anticancer and promotion of apoptosis efficacy.
Animal model	Mice bearing SW620 or HepG2 tumors.
Formulation & Dosage	Dissolved in 35% (v/v) polyethylene glycol solution containing 5% (v/v) DMSO; 100 mg/kg; i.p.
References	Clin Cancer Res. 2011 Jul 1;17(13):4439-50; Clin Exp Med. 2014 May;14(2):203-13.

In Vitro

In vitro activity: SKLB1002 shows strikingly lower cytotoxicity on normal human cells L-02. SKLB1002 significantly inhibits HUVEC proliferation, migration, invasion, and tube formation, by inhibiting VEGF-induced phosphorylation of VEGFR2 kinase and the downstream protein kinases including ERK, FAK, and Src.

Kinase Assay: Kinase inhibition is measured by the use of radiometric assays conducted by Kinase Profiler service. Briefly, in the presence or absence of SKLB1002, VGFR2 (5–10 mU) is incubated in 25-μL reaction solution containing 8 mmol/L 3-(N-morpholino)propanesulfonic acid (MOPS), pH 7.0, 0.2 mmol/L EDTA, 0.33 mg/mL myelin basic protein, 10 mmol/L Mg acetate, and γ-[33P]ATP. After incubation for 40 minutes at room temperature, the reaction is stopped and 10 μL of the reaction solution is then spotted onto a P30 filtermat and washed 3 times for 5 minutes in 75 mmol/L phosphoric acid and once in methanol prior to scintillation counting.

Cell Assay: Cell proliferation is measured using MTT assay. Various cells including HUVECs, L-02, B16-F10, HepG2, and SW620 are treated with indicated concentrations of SKLB1002 for 24 hours. Vandetanib and sunitinib serve as positive controls. Each assay is replicated 3 times.

In Vivo

In the zebrafish embryos, SKLB1002 remarkably blocks the formation of embryonic and tumor-induced angiogenesis with no or least impact on normal cell proliferation. In athymic mice bearing SW620 or HepG2 xenografts, SKLB1002 (100 mg/kg daily, i.p.) causes significant inhibition of tumor growth, inhibits tumor angiogenesis and induces tumor apoptosis. In 4T1 and CT26 tumor model, SKLB1002 and local hyperthermia produce a synergistic antiangiogenesis, anticancer and promotion of apoptosis efficacy.

Animal model

Mice bearing SW620 or HepG2 tumors.

Formulation & Dosage

Dissolved in 35% (v/v) polyethylene glycol solution containing 5% (v/v) DMSO; 100 mg/kg; i.p.

References

Clin Cancer Res. 2011 Jul 1;17(13):4439-50; Clin Exp Med. 2014 May;14(2):203-13.

CAS NO:	1225451-84-2
规格:	≥98%

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