PF-06424439
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Hodoodo CAT#: H522401

CAS#: 1469284-78-3 (free base)

Description: PF-06424439 is a potent and selective Diacylglycerol Acyltransferase 2 ( DGAT2) inhibitor with DGAT2 IC50 ± SEM (nM) (human/rat/dog) 14 ± 1/38 ± 4/16 ± 1. PF-06424439 demonstrated excellent ADMET properties and decreased circulating and hepatic lipids when orally administered to dyslipidemic rodent models. PF-06424439 inhibited DGAT2 of different species (human, rat, and dog) with similar potency. Among related acyltransferases, no significant inhibition was observed for PF-06424439 (up to 50 μM) against human MGAT2 or MGAT3, DGAT1, or mouse MGAT1, indicating a high selectivity (>2000-fold) against these enzymes.

Chemical Structure

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PF-06424439
CAS# 1469284-78-3 (free base)
Instruction

Theoretical Analysis

Hodoodo Cat#: H522401
Name: PF-06424439
CAS#: 1469284-78-3 (free base)
Chemical Formula: C22H26ClN7O
Exact Mass: 439.19
Molecular Weight: 439.940
Elemental Analysis: C, 60.06; H, 5.96; Cl, 8.06; N, 22.29; O, 3.64

Price and Availability

Size Price Availability Quantity
50mg USD 950 2 Weeks
100mg USD 1650 2 Weeks
200mg USD 2650 2 Weeks
500mg USD 3650 2 Weeks
1g USD 4950 2 Weeks
2g USD 7950 2 Weeks
Bulk inquiry

Related CAS #: 1469284-78-3 (free base)   1469284-80-7 (HCl)   1469284-79-4 (mesylate),  

Synonym: PF-06424439; PF06424439; PF 06424439; PF-6424439; PF-6424439; PF 6424439.

IUPAC/Chemical Name: (R)-(1-(2-(1-(4-chloro-1H-pyrazol-1-yl)cyclopropyl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone

InChi Key: PZHNKPBYOPQTRG-OAHLLOKOSA-N

InChi Code: InChI=1S/C22H26ClN7O/c23-16-12-24-30(14-16)22(7-8-22)21-25-17-5-6-18(26-19(17)27-21)29-11-3-4-15(13-29)20(31)28-9-1-2-10-28/h5-6,12,14-15H,1-4,7-11,13H2,(H,25,26,27)/t15-/m1/s1

SMILES Code: O=C([C@H]1CN(C2=CC=C3C(NC(C4(N5N=CC(Cl)=C5)CC4)=N3)=N2)CCC1)N6CCCC6

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target: PF-06424439 is a selective imidazopyridine diacylglycerol acyltransferase 2 (DGAT2) inhibitor with an IC50 of 14 nM that is a slowly reversible, time-dependent inhibitor, which inhibits DGAT2 in a noncompetitive mode with respect to the acyl-CoA substrate.
In vitro activity: The effect of PF-06424439, a selective DGAT2 inhibitor, on MCF7 breast cancer cells exposed to X-rays was evaluated. The results demonstrated that 72 h of PF-06424439 treatment reduced LD (lipid droplets) content and inhibited cell migration, without affecting cell proliferation. Interestingly, PF-06424439 pre-treatment followed by radiation was able to enhance radiosensitivity of MCF7 cells. These findings suggest that PF-06424439 pre-treatment coupled to X-ray exposure might potentiate breast cancer cell radiosensitivity and potentially improve the radiotherapy effectiveness. Reference: Int J Mol Sci. 2021 Sep 18;22(18):10102. https://pubmed.ncbi.nlm.nih.gov/34576263/
In vivo activity: The effects of DGAT1 and DGAT2 inhibition, alone or in combination, on dietary TAG absorption and diarrhea in mice were investigated by using a selective DGAT1 inhibitor (PF-04620110) and DGAT2 inhibitor (PF-06424439). To further understand relationship between diarrhea and changes in DGAT activity, we examined dose‐dependent effects of DGAT inhibitors in mice. Simultaneous administration of a lower‐dose DGAT1 (0.03 mg/kg) inhibitor, which did not produce maximal effects on intestinal TAG secretion, and the DGAT2 inhibitors significantly decreased plasma radioactivity. These findings suggest that DGAT-mediated intestinal TAG synthesis is a vital step for maintaining intestinal barrier integrity under HFD (high-fat diet) feeding. Reference: Physiol Rep. 2020 Aug;8(15):e14542. https://pubmed.ncbi.nlm.nih.gov/32786057/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 70.0 159.11
H2O 70.0 159.11

Preparing Stock Solutions

The following data is based on the product molecular weight 439.94 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Nisticò C, Pagliari F, Chiarella E, Fernandes Guerreiro J, Marafioti MG, Aversa I, Genard G, Hanley R, Garcia-Calderón D, Bond HM, Mesuraca M, Tirinato L, Spadea MF, Seco JC. Lipid Droplet Biosynthesis Impairment through DGAT2 Inhibition Sensitizes MCF7 Breast Cancer Cells to Radiation. Int J Mol Sci. 2021 Sep 18;22(18):10102. doi: 10.3390/ijms221810102. PMID: 34576263; PMCID: PMC8466244. 2. Takemoto K, Fukasaka Y, Yoshimoto R, Nambu H, Yukioka H. Diacylglycerol acyltransferase 1/2 inhibition induces dysregulation of fatty acid metabolism and leads to intestinal barrier failure and diarrhea in mice. Physiol Rep. 2020 Aug;8(15):e14542. doi: 10.14814/phy2.14542. PMID: 32786057; PMCID: PMC7422801.
In vitro protocol: 1. Nisticò C, Pagliari F, Chiarella E, Fernandes Guerreiro J, Marafioti MG, Aversa I, Genard G, Hanley R, Garcia-Calderón D, Bond HM, Mesuraca M, Tirinato L, Spadea MF, Seco JC. Lipid Droplet Biosynthesis Impairment through DGAT2 Inhibition Sensitizes MCF7 Breast Cancer Cells to Radiation. Int J Mol Sci. 2021 Sep 18;22(18):10102. doi: 10.3390/ijms221810102. PMID: 34576263; PMCID: PMC8466244.
In vivo protocol: 1. Takemoto K, Fukasaka Y, Yoshimoto R, Nambu H, Yukioka H. Diacylglycerol acyltransferase 1/2 inhibition induces dysregulation of fatty acid metabolism and leads to intestinal barrier failure and diarrhea in mice. Physiol Rep. 2020 Aug;8(15):e14542. doi: 10.14814/phy2.14542. PMID: 32786057; PMCID: PMC7422801.

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1: Futatsugi K, Kung DW, Orr ST, Cabral S, Hepworth D, Aspnes G, Bader S, Bian J,
Boehm M, Carpino PA, Coffey SB, Dowling MS, Herr M, Jiao W, Lavergne SY, Li Q,
Clark RW, Erion DM, Kou K, Lee K, Pabst BA, Perez SM, Purkal J, Jorgensen CC,
Goosen TC, Gosset JR, Niosi M, Pettersen JC, Pfefferkorn JA, Ahn K, Goodwin B.
Discovery and Optimization of Imidazopyridine-Based Inhibitors of Diacylglycerol
Acyltransferase 2 (DGAT2). J Med Chem. 2015 Sep 24;58(18):7173-85. doi:
10.1021/acs.jmedchem.5b01006. PubMed PMID: 26349027.