CC-90001 (CC90001; CC 90001) is a novel, potent and selective inhibitor of c-Jun N-terminal kinase (JNK) with potential anti-fibrotic activity. With IC50 values of 11 and 31 nM, it inhibits JNK1/2. CC-90001 has a low nanomolar JNK inhibitory potency, broad kinome selectivity, and the capacity to prevent cellular phosphorylation of the direct JNK substrate c-Jun. Regarding the physicochemical characteristics, CC-90001 also showed excellent systemic exposure after oral dosing, enabling in vivo efficacy studies and the choice of CC-90001 for clinical development. Patients with idiopathic pulmonary fibrosis are currently participating in Phase II clinical trials for CC-90001 (NCT03142191).

Physicochemical Properties

Molecular Formula	C16H27N5O2
Molecular Weight	321.41788315773
Exact Mass	321.22
Elemental Analysis	C, 59.79; H, 8.47; N, 21.79; O, 9.96
CAS #	1403859-14-2
Related CAS #	1946833-77-7 (HCl);1403859-14-2;1946833-89-1;1946833-91-5 (mesylate); 1946833-97-1 (tartarte); 1946833-81-3 (lactate); 1946833-85-7 (citrate); 1946833-97-1 （fumarate);
PubChem CID	71237511
Appearance	White to yellow solid powder
LogP	2.3
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	5
Heavy Atom Count	23
Complexity	412
Defined Atom Stereocenter Count	3
SMILES	C[C@@H]1CC[C@H](C[C@H]1O)NC2=NC(=NC=C2C(=O)N)NC(C)(C)C
InChi Key	QBBRJRLJWXRSHQ-CKYFFXLPSA-N
InChi Code	InChI=1S/C16H27N5O2/c1-9-5-6-10(7-12(9)22)19-14-11(13(17)23)8-18-15(20-14)21-16(2,3)4/h8-10,12,22H,5-7H2,1-4H3,(H2,17,23)(H2,18,19,20,21)/t9-,10-,12-/m1/s1
Chemical Name	2-(tert-butylamino)-4-[[(1R,3R,4R)-3-hydroxy-4-methylcyclohexyl]amino]pyrimidine-5-carboxamide
Synonyms	CC 90001; CC-90001; CC90001
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; JNK2
ln Vitro	In cell tests, CC-90001 suppresses LPS-induced c-jun phosphorylation with an EC50 of 480 nM [1]. JNK1 is 12.9 times more efficiently inhibited by CC-90001 than JNK2 is by the use of JNK1 and JNK2 knockout fibroblasts [1].
ln Vivo	A 48% reduction in collagen and a 53% reduction in alpha-smooth actin (α-SMA) in an adipose collagen model demonstrate that CC-90001 (3 mg/kg bid) inhibits the development of fibrosis [1]. CC-90001 lowers lung collagen extraction markers and disease-causing elevations in α-SMA to levels close to baseline in a home dust mite pulmonary fibrosis model [1].
References	[1]. CC-90001, a Second Generation Jun N-Terminal Kinase (JNK) Inhibitor for the Treatment of Idiopathic Pulmonary Fibrosis. American Journal of Respiratory and Critical Care Medicine 2017; 195:A5409. [2]. Therapeutic targets in idiopathic pulmonary fibrosis. Respir Med. 2017 Oct;131:49-57.
Additional Infomation	JNK1 Inhibitor BMS-986360 is an orally bioavailable, second-generation inhibitor of c-Jun N-terminal kinase 1 (JNK-1; JNK1; mitogen-activated protein kinase 8; MAPK8), with potential antineoplastic, anti-inflammatory and anti-fibrotic activities. Upon oral administration, JNK1 inhibitor BMS-986360 selectively targets, binds to and inhibits the activity of JNK1. Inhibition of JNK1-mediated mitogen-activated protein kinase (MAPK)-signaling pathways induces cell cycle arrest and apoptosis, decreases migration and invasion, and inhibits proliferation in JNK1-overexpressing cancer cells. Inhibition of JNK1-mediated pathways may also decrease fibrosis. JNK1, a member of the MAPK family and stress-activated protein, plays a role in the MAPK-mediated signaling pathway. It is often dysregulated in cancer cells and fibrosis.

Solubility Data

Solubility (In Vitro)

DMSO: ~125 mg/mL (~388.9 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.47 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 20.8 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: ≥ 2.08 mg/mL (6.47 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 20.8 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: ≥ 2.08 mg/mL (6.47 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.1112 mL	15.5560 mL	31.1119 mL
	5 mM	0.6222 mL	3.1112 mL	6.2224 mL
	10 mM	0.3111 mL	1.5556 mL	3.1112 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.