AS602801 (also known as Bentamapimod and PGL5001) is a novel, potent and ATP-competitive JNK (c-Jun N-terminal Kinase) inhibitor with IC50 values of 80 nM, 90 nM, and 230 nM for JNK1, JNK2, and JNK3, respectively. It functions as a JNK inhibitor and could decrease the induced endometriosis in the baboon without having a significant impact on the length of the cycle, the levels of serum reproductive hormones, or any significant adverse effects on the endocrine system. Preglem's AS602801 Phase 2 Trial (NCT01630252) is now complete.

Physicochemical Properties

Molecular Formula	C25H23N5O2S
Molecular Weight	457.55
Exact Mass	457.157
Elemental Analysis	C, 65.63; H, 5.07; N, 15.31; O, 6.99; S, 7.01
CAS #	848344-36-5
Related CAS #	848344-36-5
PubChem CID	10195250
Appearance	Light yellow to yellow solid powder
Density	1.3±0.1 g/cm3
Boiling Point	666.5±65.0 °C at 760 mmHg
Flash Point	356.9±34.3 °C
Vapour Pressure	0.0±2.0 mmHg at 25°C
Index of Refraction	1.667
LogP	2.71
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	7
Heavy Atom Count	33
Complexity	660
Defined Atom Stereocenter Count	0
SMILES	N#CC(C1C=CN=C(OCC2C=CC(CN3CCOCC3)=CC=2)N=1)C1SC2C(=CC=CC=2)N=1
InChi Key	XCPPIJCBCWUBNT-UHFFFAOYSA-N
InChi Code	InChI=1S/C25H23N5O2S/c26-15-20(24-28-22-3-1-2-4-23(22)33-24)21-9-10-27-25(29-21)32-17-19-7-5-18(6-8-19)16-30-11-13-31-14-12-30/h1-10,20H,11-14,16-17H2
Chemical Name	2-(1,3-benzothiazol-2-yl)-2-[2-[[4-(morpholin-4-ylmethyl)phenyl]methoxy]pyrimidin-4-yl]acetonitrile
Synonyms	AS602801; AS-602801; AS 602801; Bentamapimod; PGL5001; PGL-5001; PGL 5001
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

Targets	JNK1 (IC50 = 80 nM); JNK2 (IC50 = 90 nM); JNK3 (IC50 = 230 nM)
ln Vitro	In vitro, AS602801 demonstrates cytotoxicity against both serum-cultured non-stem cancer cells and cancer stem cells derived from human pancreatic cancer, non-small cell lung cancer, ovarian cancer, and glioblastoma at concentrations that do not impair the viability of healthy human fibroblasts. Additionally, AS602801 prevents cancer stem cells that have survived treatment from renewing themselves and starting tumors[2].
ln Vivo	Systemic administration of AS602801 at a dose and schedule that did not negatively impact the health of the tumor-bearing mice reduced the number of cancer stem cells in established xenograft tumors[2].
Enzyme Assay	AS602801 (also known as Bentamapimod and PGL5001) is a novel, potent and ATP-competitive JNK (c-Jun N-terminal Kinase) inhibitor with IC50 values of 80 nM, 90 nM, and 230 nM for JNK1, JNK2, and JNK3, respectively. It functions as a JNK inhibitor and can lessen the surface area and volume of induced endometriosis in baboons without having a significant impact on cycle length or serum levels of reproductive hormones or having any significant adverse effects on the endocrine system.
Cell Assay	Human IMR90 normal fibroblasts and human cancer cells PANC-1, A2780, and A549 are subjected to a 3-day treatment period with or without bentamapimod (AS 602801) at the indicated concentrations (2.5, 5, or 7.5 μM). Using trypan blue as a vital dye, researchers were able to count the number of viable cells (left panels) and the percentage of dead cells (right panels)[2].
Animal Protocol	Mice: The silastic capsule containing 8 μg of estradiol is implanted subcutaneously into the 5-week-old athymic (ncr/nude) ovariectomized mice after isoflurane anesthesia. Twenty-four hours later, mice were injected subcutaneously or intraperitoneally with a phosphate-buffered saline (PBS) suspension containing 8 to 10 fragments of human endometrial tissue per mouse (biopsies taken from volunteers or patients) on the ventral midline just below the umbilicus. Tissue fragments are cultured as organs for 24 hours prior to injection while being treated with 1 nM estradiol, PR, or MPA. Bentamapimod (AS 602801) is first administered orally 10 to 12 days after tissue injection. MPA is administered twice weekly by tuberculin syringe injections (200 mg/kg) along the right flank, and progesterone is administered via a slow-release silastic capsule containing 25 μg PR. Gavage administration of bentamapimod (AS 602801) is carried out for 30 days at doses of 10 mg/kg and 30 mg/kg/animal. In order to directly examine the size and number of lesions, mice are once more given general anesthesia and sacrificed by cervical dislocation after the course of treatment is complete. In order to facilitate further analysis, excised lesions from uteri are weighed and measured[3].
References	[1]. Recent progress in the design, study, and development of c-Jun N-terminal kinase inhibitors as anticanceragents. Chem Biol. 2014 Nov 20;21(11):1433-43. [2]. The novel JNK inhibitor AS602801 inhibits cancer stem cells in vitro and in vivo. Oncotarget. 2016 May 10;7(19):27021-32. [3]. Bentamapimod (JNK Inhibitor AS602801) Induces Regression of Endometriotic Lesions in Animal Models. Reprod Sci. 2016 Jan;23(1):11-23.

Solubility Data

Solubility (In Vitro)

DMSO: ~10 mM Water: N/A Ethanol: N/A

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 0.83 mg/mL (1.81 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 + to the above solution and mix evenly; then add 450 μL of 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1856 mL	10.9278 mL	21.8555 mL
	5 mM	0.4371 mL	2.1856 mL	4.3711 mL
	10 mM	0.2186 mL	1.0928 mL	2.1856 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.