ISA-2011B is an inhibitor (blocker/antagonist) of PIP5K1α and has anti-cancer activity.

Physicochemical Properties

Molecular Formula	C22H18CLN3O4
Molecular Weight	423.85
Exact Mass	423.098
CAS #	1395347-24-6
PubChem CID	49853637
Appearance	White to off-white solid powder
Density	1.6±0.1 g/cm3
Boiling Point	714.9±60.0 °C at 760 mmHg
Flash Point	386.1±32.9 °C
Vapour Pressure	0.0±2.3 mmHg at 25°C
Index of Refraction	1.762
LogP	2.23
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	1
Heavy Atom Count	30
Complexity	737
Defined Atom Stereocenter Count	2
SMILES	CN1CC(=O)N2[C@H](C1=O)CC3=CC4=C(C=C3[C@H]2C5=CNC6=C5C=C(C=C6)Cl)OCO4
InChi Key	FSEZESVJDPKRDS-UWJYYQICSA-N
InChi Code	InChI=1S/C22H18ClN3O4/c1-25-9-20(27)26-17(22(25)28)4-11-5-18-19(30-10-29-18)7-13(11)21(26)15-8-24-16-3-2-12(23)6-14(15)16/h2-3,5-8,17,21,24H,4,9-10H2,1H3/t17-,21-/m0/s1
Chemical Name	(2S,8S)-2-(5-chloro-1H-indol-3-yl)-6-methyl-13,15-dioxa-3,6-diazatetracyclo[8.7.0.03,8.012,16]heptadeca-1(17),10,12(16)-triene-4,7-dione
Synonyms	ISA-2011B ISA 2011B ISA2011B
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	Compared with the vehicle-treated control, the proliferation rates of PC-3 cells were considerably reduced to 58.77%, 48.65%, and 21.62%, respectively, after treatment with 10, 20, and 50 μM ISA-2011B. ISA-2011B has the highest binding affinity for PIP5K1α and MAP/microtubule affinity-regulated kinases 1 and 4 (MARK1 and MARK4) among 460 kinases. ISA-2011B treatment suppressed 78.6% of PIP5K1α expression in PC-3 cells [1]. ISA-2011B induced a considerable decrease of AR-V7 and CDK1 in the nucleus and cytoplasm of 22Rv1 cells. ISA-2011B therapy also reduces AR expression in the nucleus without diminishing cytoplasmic AR[2].
ln Vivo	ISA-2011B effectively reduces the growth of tumor cells in xenograft mice and is mediated by inhibiting PIP5K1α-related PI3K/AKT and its downstream survival, proliferation and invasion pathways [1]. Overexpression of AR-V7 raises PIP5K1α and promotes rapid PCa growth in xenograft mice, whereas inhibition of PIP5K1α by its inhibitor ISA-2011B decreases the growth and invasiveness of xenograft tumors overexpressing AR-V7. ISA-2011B inhibits the PIP5K1α-dependent protein stability of AR-V7, consequently decreasing the invasive growth of AR-V7-high tumors in xenograft mice [2].
References	[1]. The role of PI3K/AKT-related PIP5K1α and the discovery of its selective inhibitor for treatment of advanced prostate cancer. Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):E3689-98. [2]. Targeted suppression of AR-V7 using PIP5K1α inhibitor overcomes MDV3100 resistance in prostate cancer cells. Oncotarget. 2016 Sep 27;7(39):63065-63081.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~235.93 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.90 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.5 mg/mL (5.90 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.90 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 4 mg/mL (9.44 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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	2.3593 mL	11.7966 mL	23.5933 mL
	5 mM	0.4719 mL	2.3593 mL	4.7187 mL
	10 mM	0.2359 mL	1.1797 mL	2.3593 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.