Samuraciclib HCl (ICEC-0942; PPDA001; CT-7001), the hydrochloride salt of Samuraciclib, is a novel, potent, orally bioavailable and selective CDK7 inhibitor with potential anticancer activity. Its IC50 values are 41 nM and 578 nM, respectively, for CDK2/cycE1 and CDK7/CycH/MAT1. Cancer treatment may be possible with it. IC50 values for CDK1, CDK2, CDK5, and CDK9 were 45-, 15-, 230-, and 30-fold higher than that of CDK7, which it selectively inhibits at a 40nM concentration. GI50 values range between 0.2 and 0.3 µM, indicating that a broad spectrum of cancer types are sensitive to CDK7 inhibition in vitro.

Physicochemical Properties

Molecular Formula	C22H31CLN6O
Molecular Weight	430.974143266678
Exact Mass	430.22
Elemental Analysis	C, 61.31; H, 7.25; Cl, 8.23; N, 19.50; O, 3.71
CAS #	1805789-54-1
Related CAS #	Samuraciclib hydrochloride hydrate;Samuraciclib hydrochloride hydrate;Samuraciclib;1805833-75-3
PubChem CID	91844732
Appearance	White to light yellow solid powder
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	7
Heavy Atom Count	30
Complexity	500
Defined Atom Stereocenter Count	2
SMILES	CC(C)C1=C2N=C(C=C(N2N=C1)NCC3=CC=CC=C3)NC[C@H]4CCNC[C@@H]4O.Cl
InChi Key	YMNPLAHCOLEZJE-ZFNKBKEPSA-N
InChi Code	InChI=1S/C22H30N6O.ClH/c1-15(2)18-13-26-28-21(25-11-16-6-4-3-5-7-16)10-20(27-22(18)28)24-12-17-8-9-23-14-19(17)29;/h3-7,10,13,15,17,19,23,25,29H,8-9,11-12,14H2,1-2H3,(H,24,27);1H/t17-,19+;/m1./s1
Chemical Name	(3R,4R)-4-[[[7-(benzylamino)-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol;hydrochloride
Synonyms	PPDA-001; PPDA-001; PPDA-001; GTPL 9903; GTPL9903; GTPL-9903; ICEC0942; ICEC 0942; ICEC-0942; CT7001; CT 7001;CT-7001
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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.
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	CDK7 (IC50 = 41 nM); CDK2 (IC50 = 578 nM); CDK1 (IC50 = 1.8 μM); CDK4 (IC50 = 49 μM); CDK5 (IC50 = 9.4 μM); CDK6 (IC50 = 41 nM); CDK7 (IC50 = 34 μM); CDK9 (IC50 = 1.2 μMM)
ln Vitro	ICEC0942 inhibits CDK7 in a wide range of cancer types, with GI50 values ranging from 0.2 to 0.3 µM. In the MCF7 breast cancer cell line, ICEC0942 dose- and time-dependently inhibits the phosphorylation of PolII, CDK1, CDK2, and RB (retinoblastoma). ICEC0942 stimulates apoptosis and cell cycle arrest by preventing CDK7 substrate phosphorylation[1].
ln Vivo	ICEC0942 has strong anti-tumor effects in colorectal and breast cancer xenografts. Male CD1 mice are given 10 mg/kg ICEC0942 intravenously (IV), subcutaneously (SC), or orally (PO) for pharmacokinetic purposes. The biphasic decline in ICEC0942 levels in plasma suggests that the compound is rapidly distributed into tissues. Cl(plasma) is measured at 78 ml/min/kg in male CD1 mice after receiving ICEC0942 intraperitoneally at a dose of 10 mg/kg. Ratio of blood to plasma (Bl/Pl) is 1.81. ICEC0942 has a moderate half-life for this species, lasting 1.9 hours. One PO administration (100 mg/kg) of ICEC0942 results in only a small amount of metabolization—13.5%—after two and four hours. Comparing oral bioavailability (F%) at 30% with single PO and IV administration at 10 mg/kg for exposure (AUCt). The median Tmax for PO administration is two hours, and a higher dose has no effect. AUCt, or the total exposure over time, and Cmax have a linear relationship with dose within this dose range. Six hours after administration, there is a noticeable build-up of ICEC0942 in the tumors of tumor-bearing mice. Tumor ICEC0942 levels are not as high as plasma levels[1].
Animal Protocol	seven-week old female nu/nu-BALB/c athymic nude mice with tumour xenograft 100 mg/kg/day PO
References	[1]. ICEC0942, an Orally Bioavailable Selective Inhibitor of CDK7 for Cancer Treatment. Mol Cancer Ther. 2018 Jun;17(6):1156-1166. [2]. Inhibitor Selectivity for Cyclin-Dependent Kinase 7: A Structural, Thermodynamic, and Modelling Study. ChemMedChem. 2017 Mar 7;12(5):372-380.

Solubility Data

Solubility (In Vitro)

DMSO: 86~100 mg/mL (199.6~232.0 mM) Ethanol: 15 mg/mL (~34.8 mM) Water: 86 mg/mL (~199.6 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.80 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 (5.80 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 (5.80 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: 100 mg/mL (232.03 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.3203 mL	11.6017 mL	23.2035 mL
	5 mM	0.4641 mL	2.3203 mL	4.6407 mL
	10 mM	0.2320 mL	1.1602 mL	2.3203 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.