LDC4297 HCl is a selective inhibitor of CDK7 with IC50 of 0.13 nM. LDC4297 HCl inhibits human cytomegalovirus (HCMV) replication with EC50 of 24.5 nM. LDC4297 HCl displays a broad-spectrum antiviral effect with EC50s of 0.02-1.21 μM against herpesviruses, adenoviruses, poxviruses, retroviruses and orthomyxoviruses. LDC4297 HCl may be utilized in infection research.

Physicochemical Properties

Molecular Formula	C23H29CLN8O
Molecular Weight	468.982362508774
Exact Mass	468.215
CAS #	2319747-14-1
Related CAS #	LDC4297;1453834-21-3
PubChem CID	137958370
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	7
Heavy Atom Count	33
Complexity	594
Defined Atom Stereocenter Count	0
SMILES	C(C1C=NN2C(=NC(OC3CNCCC3)=NC=12)NCC1C=CC=CC=1N1N=CC=C1)(C)C.Cl
InChi Key	CEUJJAKJRBKKSL-UHFFFAOYSA-N
InChi Code	InChI=1S/C23H28N8O.ClH/c1-16(2)19-15-27-31-21(19)28-23(32-18-8-5-10-24-14-18)29-22(31)25-13-17-7-3-4-9-20(17)30-12-6-11-26-30;/h3-4,6-7,9,11-12,15-16,18,24H,5,8,10,13-14H2,1-2H3,(H,25,28,29);1H
Chemical Name	2-piperidin-3-yloxy-8-propan-2-yl-N-[(2-pyrazol-1-ylphenyl)methyl]pyrazolo[1,5-a][1,3,5]triazin-4-amine;hydrochloride
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 and light.
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 0.13 nM (IC50) 166v VP22-GFP 0.02 μM (EC50) 01-6332 0.27 μM (EC50) HIV-1 (NL4.3 strain) 1.04 μM (EC50) 4LIG7 1.13 μM (EC50)
ln Vitro	LDC4297 hydrochloride (0-10 μM; 6 d) dose-dependently suppresses HCMV replication with an EC50 value of 24.5 nM[1]. LDC4297 hydrochloride (0-10 μM; 4 d) has a GI50 value of 4.5 μM and exhibits anti-proliferative activity against primary cultures of human fibroblasts (HFF)[1]. Via a complex mechanism of action that includes interfering with virus-induced Rb phosphorylation, LDC4297 hydrochloride (20 μM; 12-96 h) has anti-HCMV activity[1]. Broad antiviral activities against HCMV, GPCMV, MCMV, HVV-6A, HSV-1, HSV-2, VZV, EBV, HAdV-2, Vaccinia virus, HIV-1 (nl4-3), HIV-1 (4LIG7), and Influenza A virus are demonstrated by LDC4297 hydrochloride (0-10 μM; 7 d), with EC50 values of 0.02, 0.05, 0.07, 0.04, 0.02, 0.27, 0.06, 1.21, 0.25, 0.77, 1.04, 1.13, and 0.99 μM, respectively[1].
ln Vivo	Pharmacokinetic analyses of LDC4297 hydrochloride (100 mg/kg; po once) are encouraging[1].
Cell Assay	Western Blot Analysis[1] Cell Types: Primary cultures of fibroblasts derived from human (HFF) with virus infection Tested Concentrations: 20 μM Incubation Duration: 12, 24, 48 and 96 hrs (hours) Experimental Results: demonstrated inhibitory effect towards viral protein synthesis at the stage of immediate early (IE) gene expression and the drug-mediated reduction of IE1p72 levels partially recovered over time. Exerted an inhibitory effect on human cytomegalovirus (HCMV) induced an up-regulation of protein expression or protein phosphorylation, and decreased Rb expression in the uninfected control cells at 24 h.
Animal Protocol	Animal/Disease Models: CD1 mice[1] Doses: 100 mg/kg Route of Administration: po (oral gavage); 100 mg/kg once Experimental Results: demonstrated a half-life (t1/2z) of 1.6 h, and the time to a mean peak plasma concentration of 1297.6 ng/mL is reached 0.5 h after administration with a continued presence in plasma for at least 8 h and a bioavailability of 97.7%.
References	[1]. A novel CDK7 inhibitor of the Pyrazolotriazine class exerts broad-spectrum antiviral activity at nanomolar concentrations. Antimicrob Agents Chemother. 2015 Apr;59(4):2062-71.

Solubility Data

Solubility (In Vitro)

DMSO : 100 mg/mL (213.23 mM)

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1323 mL	10.6614 mL	21.3229 mL
	5 mM	0.4265 mL	2.1323 mL	4.2646 mL
	10 mM	0.2132 mL	1.0661 mL	2.1323 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.