HIF-PHD-IN-1 is a dye for the hypoxia-inducible factor tyrosine kinase foam reflux platforming enzyme domain (HIF-PHD) with apoptosis pathway activity. The IC50 for inhibiting hHIF-PHD2 is 54 nM. IN-1 is a promising active molecule in renal anemia research.

Physicochemical Properties

Molecular Formula	C17H12CL2N6O3
Molecular Weight	419.221580505371
Exact Mass	418.034
CAS #	1567657-46-8
PubChem CID	137092773
Appearance	Off-white to light yellow solid powder
LogP	2.5
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	4
Heavy Atom Count	28
Complexity	679
Defined Atom Stereocenter Count	1
SMILES	N1(C2NC(=O)C3N([C@H](C4=CC(Cl)=CC=C4Cl)C)N=CC=3N=2)C=C(C(O)=O)C=N1
InChi Key	BJMKDEGQDAVFGT-QMMMGPOBSA-N
InChi Code	InChI=1S/C17H12Cl2N6O3/c1-8(11-4-10(18)2-3-12(11)19)25-14-13(6-21-25)22-17(23-15(14)26)24-7-9(5-20-24)16(27)28/h2-8H,1H3,(H,27,28)(H,22,23,26)/t8-/m0/s1
Chemical Name	1-[1-[(1S)-1-(2,5-dichlorophenyl)ethyl]-7-oxo-6H-pyrazolo[4,3-d]pyrimidin-5-yl]pyrazole-4-carboxylic acid
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

ln Vivo	HIF-PHD-IN-1 (compound 19) (0.5-2 mg/kg; orally, once day for 4 weeks) increases hemoglobin levels in anemic rats [1]. HIF-PHD-IN-1 (10 mg/kg; single oral dose) increases serum erythropoietin (EPO) concentration in SD rats 8 hours after delivery [1]. HIF-PHD-IN-1 (1 mg/kg; oral) showed high absorption (F=77%) in male SD rats [1].
Animal Protocol	Animal/Disease Models: Male SD rat, five-sixths of the kidneys were removed [1] Doses: 0.5, 1, 2 mg/kg Route of Administration: Oral one time/day for 4 weeks Experimental Results: The treated group started from the 2nd week and Hemoglobin levels improved by 1 and 2 (mg/kg)/day starting in week 1, respectively. Animal/Disease Models: Male SD rat[1] Doses: 1 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: Single oral or intravenous (iv) (iv)injection Experimental Results: Cmax=1839 ng/mL (oral); Cmax=12357ng/mL (iv); F=77%.
References	[1]. Pyrazolo[4,3- d]pyrimidine Derivatives as a Novel Hypoxia-Inducible Factor Prolyl Hydroxylase Domain Inhibitor for the Treatment of Anemia. ACS Med Chem Lett. 2020 Jun 4; 11(7): 1416-1420.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~238.54 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.96 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.3854 mL	11.9269 mL	23.8538 mL
	5 mM	0.4771 mL	2.3854 mL	4.7708 mL
	10 mM	0.2385 mL	1.1927 mL	2.3854 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.