Tasisulam

For research use only.

Catalog No.S7326 Synonyms: LY573636

1 publication

Molecular Weight(MW): 415.11

Tasisulam is an antitumor agent and an apoptosis inducer via the intrinsic pathway. Phase 3.

Selleck's Tasisulam has been cited by 1 publication

Skin Pharmacol Physiol, 2016, 29(6):281-290

PubMed: 28013301

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Biological Activity

Description

Tasisulam is an antitumor agent and an apoptosis inducer via the intrinsic pathway. Phase 3.

Targets

Caspase ^[1]

In vitro

Tasisulam inhibits growth of various human leukemia and lymphoma cell lines with ED50 ranging from 7 to 40 μM. LY573636 also induces apoptosis in HL60, Reh, and MD901 cells, mainly by loss of mitochondrial membrane potential and induction of reactive oxygen species. ^[1] In addition, Tasisulam also produce antiproliferative activities in more than 70% of the 120 cell lines tested with EC50 of less than 50 μM. Tasisulam induces G2–M accumulation and subsequent apoptosis in Calu-6 and A-375 cells. In vitro, Tasisulam also inhibits VEGF-, FGF- and EGF-induced endothelial cord formation with EC50 of 47, 103, and 34 nM, respectively. ^[2]

In vivo

Tasisulam induces morphologic features of vascular normalization, including increased pericyte coverage and decreased hypoxia in vivo. Tasisulam (25 or 50 mg/kg, i.v.) displays dose-dependent antitumor activity, induces apoptosis, and normalizes tumor-associated vasculature in the Calu-6 non–small cell lung xenograft model. Besides, Tasisulam displays potent antitumor activity across a range of in vivo xenografts, including colorectal (HCT-116), melanoma (A-375), gastric (NUGC-3), leukemia (MV-4-11), and pancreatic (QGP-1). ^[2]

Protocol

Cell Research: ^[1]	- Collapse Cell lines: B-cell acute lymphocytic leukemia (Reh, RCH, BALL1), Burkitt’s lymphoma (Daudi), diffuse large B-cell lymphoma (MD901, LY4), myeloid leukemia cell lines (HL60 and U937), Mantle cell lymphoma cell lines (NCEB1, Jeko1, and SP49). Concentrations: ~40 μM Incubation Time: 96 hours Method: Cells are treated with various concentrations of LY573636. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay is performed. Briefly, MTT is dissolved in phosphate-buffered saline (PBS) at 5 mg/mL. Approximately 1,000 cells per well are incubated in culture medium for 96 hours in 96-well plates; and then, 10 μL of the MTT solution is added. After a 4-hour incubation, 100 μL of solubilization solution (20 % sodium dodecyl sulfate [SDS]) is added, and the mixture was incubated at 37 °C for 16 hours. In this assay, MTT is cleaved to an orange formazan dye by metabolically active cells; and the absorbance of the formazan product is measured with an enzyme-linked immunoabsorbent assay (ELISA) reader at 540 nm. (Only for Reference)
Animal Research: ^[2]	- Collapse Animal Models: Calu-6 non–small cell lung xenograft model Dosages: ~50 mg/kg Administration: i.v. (Only for Reference)

Cell Research:

^[1]

- Collapse

Cell lines: B-cell acute lymphocytic leukemia (Reh, RCH, BALL1), Burkitt’s lymphoma (Daudi), diffuse large B-cell lymphoma (MD901, LY4), myeloid leukemia cell lines (HL60 and U937), Mantle cell lymphoma cell lines (NCEB1, Jeko1, and SP49).
Concentrations: ~40 μM
Incubation Time: 96 hours
Method:
Cells are treated with various concentrations of LY573636. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay is performed. Briefly, MTT is dissolved in phosphate-buffered saline (PBS) at 5 mg/mL. Approximately 1,000 cells per well are incubated in culture medium for 96 hours in 96-well plates; and then, 10 μL of the MTT solution is added. After a 4-hour incubation, 100 μL of solubilization solution (20 % sodium dodecyl sulfate [SDS]) is added, and the mixture was incubated at 37 °C for 16 hours. In this assay, MTT is cleaved to an orange formazan dye by metabolically active cells; and the absorbance of the formazan product is measured with an enzyme-linked immunoabsorbent assay (ELISA) reader at 540 nm.

(Only for Reference)

Animal Research:

^[2]

- Collapse

Animal Models: Calu-6 non–small cell lung xenograft model
Dosages: ~50 mg/kg
Administration: i.v.
(Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	83 mg/mL (199.94 mM)
	Ethanol	83 mg/mL (199.94 mM)
	Water	Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download Tasisulam SDF

Molecular Weight	415.11
Formula	C₁₁H₆BrCl₂NO₃S₂
CAS No.	519055-62-0
Storage	3 years -20°C powder
Storage	2 years -80°C in solvent
Synonyms	LY573636
Smiles	ClC1=CC(=C(C=C1)C(=O)N[S](=O)(=O)C2=CC=C(Br)S2)Cl

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Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL， Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation：Take DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，mix and clarify.

Note：1.Please make sure the liquid is clear before adding the next solvent.
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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2020-05-15)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT01209832	Terminated	Drug: Tasisulam\|Drug: Midazolam	Advanced Cancer	Eli Lilly and Company	September 2010	Phase 1
NCT01214668	Completed	Drug: LY573636-sodium\|Drug: Liposomal Doxorubicin	Solid Tumors	Eli Lilly and Company	January 2009	Phase 1
NCT00718159	Completed	Drug: LY573636-sodium	Acute Myeloid Leukemia\|Essential Thrombocythemia	Eli Lilly and Company	August 2008	Phase 1
NCT01258348	Completed	Drug: Drug: LY573636-sodium\|Drug: Sunitinib	Metastatic Renal Cell Cancer	Eli Lilly and Company	July 2008	Phase 1
NCT01215916	Completed	Drug: LY573636\|Drug: Pemetrexed	Solid Tumors	Eli Lilly and Company	February 2008	Phase 1
NCT00490451	Completed	Drug: LY573636-sodium	Sarcoma Soft Tissue	Eli Lilly and Company	August 2007	Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Tasisulam