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MedKoo Cat#: 510288 | Name: PF4136309
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

PF-4136309, also known as INCB8761, is an orally available human chemokine receptor 2 (CCR2) antagonist with potential immunomodulating and antineoplastic activities. Upon oral administration, CCR2 antagonist PF-04136309 specifically binds to CCR2 and prevents binding of the endothelium-derived chemokine ligand CLL2 (monocyte chemoattractant protein-1 or MCP1) to its receptor CCR2, which may result in inhibition of CCR2 activation and signal transduction. This may inhibit inflammatory processes as well as angiogenesis, tumor cell migration, and tumor cell proliferation.

Chemical Structure

PF4136309
PF4136309
CAS#1341224-83-6

Theoretical Analysis

MedKoo Cat#: 510288

Name: PF4136309

CAS#: 1341224-83-6

Chemical Formula: C29H31F3N6O3

Exact Mass: 568.2410

Molecular Weight: 568.59

Elemental Analysis: C, 61.26; H, 5.50; F, 10.02; N, 14.78; O, 8.44

Price and Availability

Size Price Availability Quantity
5mg USD 90.00 Ready to ship
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,250.00 Ready to ship
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Related CAS #
857679-55-1 (racemic) 1341224-83-6
Synonym
PF4136309; PF 4136309; PF-4136309; PF04136309; PF04136309; PF-04136309; INCB8761; INCB 8761; INCB-8761.
IUPAC/Chemical Name
N-(2-((S)-3-(((1r,4S)-4-hydroxy-4-(5-(pyrimidin-2-yl)pyridin-2-yl)cyclohexyl)amino)pyrrolidin-1-yl)-2-oxoethyl)-3-(trifluoromethyl)benzamide
InChi Key
ZNSVOHSYDRPBGI-LXWOLXCRSA-N
InChi Code
InChI=1S/C29H31F3N6O3/c30-29(31,32)21-4-1-3-19(15-21)27(40)36-17-25(39)38-14-9-23(18-38)37-22-7-10-28(41,11-8-22)24-6-5-20(16-35-24)26-33-12-2-13-34-26/h1-6,12-13,15-16,22-23,37,41H,7-11,14,17-18H2,(H,36,40)/t22-,23-,28-/m0/s1
SMILES Code
O=C(N1C[C@H](CC1)N[C@@]2(CC[C@@](O)(CC2)C3=CC=C(C=N3)C4=NC=CC=N4)[H])CNC(C5=CC(C(F)(F)F)=CC=C5)=O
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-4136309 is a CCR2 antagonist with IC50s of 5.2 nM, 17 nM and 13 nM for human, mouse and rat CCR2.
In vitro activity:
In addition to being a potent human CCR2 antagonist (Table 2), PF-4136309 is also a potent murine CCR2 antagonist, exhibiting IC50 values of 17 and 13 nM in mouse and rat binding assays and 16 and 2.8 nM in mouse and rat chemotaxis assays. In signaling assays, PF-4136309 is potent in inhibiting CCR2 mediated signaling events such as intracellular calcium mobilization and ERK (extracellular signal-regulated kinase) phosphorylation with IC50 values of 3.3 and 0.5 nM, respectively. Cerep screens revealed that PF-4136309 is a selective CCR2 inhibitor, showing no significant inhibitory activity at a concentration of 1 μM when tested against a panel of >50 ion channels, transporters, chemokine receptors including CCR1, CCR3, CCR5, CXCR3, and CXCR5, and additional GPCRs. In hERG patch clamp assay, PF-4136309 inhibited hERG potassium current with an IC50 of 20 μM. Reference: ACS Med Chem Lett. 2011 Oct 5;2(12):913-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018168/
In vivo activity:
The pharmacokinetics of PF-4136309 was assessed in rats and dogs (Table 4). Following iv administration of PF-4136309, the total systemic clearance was moderate in rats but low in dogs. The apparent steady-state volume of distribution (Vss) followed the same trend as in clearance, with high Vss in rats and low Vss in dogs. As a result, PF-4136309 exhibited a moderate half-life in both species after iv administration (2.5 and 2.4 h). When administered orally, PF-4136309 was absorbed rapidly, with peak concentration time (Tmax) at 1.2 h for rats and 0.25 h for dogs. A similar half-life was observed in both species between iv dosing and po dosing. PF-4136309 was well absorbed, with an oral bioavailability of 78% in both species. Reference: ACS Med Chem Lett. 2011 Oct 5;2(12):913-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018168/
Solvent mg/mL mM comments
Solubility
DMSO 5.0 8.80
Ethanol 20.0 35.20
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 568.59 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. Xue CB, Wang A, Han Q, Zhang Y, Cao G, Feng H, Huang T, Zheng C, Xia M, Zhang K, Kong L, Glenn J, Anand R, Meloni D, Robinson DJ, Shao L, Storace L, Li M, Hughes RO, Devraj R, Morton PA, Rogier DJ, Covington M, Scherle P, Diamond S, Emm T, Yeleswaram S, Contel N, Vaddi K, Newton R, Hollis G, Metcalf B. Discovery of INCB8761/PF-4136309, a Potent, Selective, and Orally Bioavailable CCR2 Antagonist. ACS Med Chem Lett. 2011 Oct 5;2(12):913-8. doi: 10.1021/ml200199c. PMID: 24900280; PMCID: PMC4018168.
In vitro protocol:
1. Xue CB, Wang A, Han Q, Zhang Y, Cao G, Feng H, Huang T, Zheng C, Xia M, Zhang K, Kong L, Glenn J, Anand R, Meloni D, Robinson DJ, Shao L, Storace L, Li M, Hughes RO, Devraj R, Morton PA, Rogier DJ, Covington M, Scherle P, Diamond S, Emm T, Yeleswaram S, Contel N, Vaddi K, Newton R, Hollis G, Metcalf B. Discovery of INCB8761/PF-4136309, a Potent, Selective, and Orally Bioavailable CCR2 Antagonist. ACS Med Chem Lett. 2011 Oct 5;2(12):913-8. doi: 10.1021/ml200199c. PMID: 24900280; PMCID: PMC4018168.
In vivo protocol:
1. Xue CB, Wang A, Han Q, Zhang Y, Cao G, Feng H, Huang T, Zheng C, Xia M, Zhang K, Kong L, Glenn J, Anand R, Meloni D, Robinson DJ, Shao L, Storace L, Li M, Hughes RO, Devraj R, Morton PA, Rogier DJ, Covington M, Scherle P, Diamond S, Emm T, Yeleswaram S, Contel N, Vaddi K, Newton R, Hollis G, Metcalf B. Discovery of INCB8761/PF-4136309, a Potent, Selective, and Orally Bioavailable CCR2 Antagonist. ACS Med Chem Lett. 2011 Oct 5;2(12):913-8. doi: 10.1021/ml200199c. PMID: 24900280; PMCID: PMC4018168.
1: Xue CB, Wang A, Han Q, Zhang Y, Cao G, Feng H, Huang T, Zheng C, Xia M, Zhang K, Kong L, Glenn J, Anand R, Meloni D, Robinson DJ, Shao L, Storace L, Li M, Hughes RO, Devraj R, Morton PA, Rogier DJ, Covington M, Scherle P, Diamond S, Emm T, Yeleswaram S, Contel N, Vaddi K, Newton R, Hollis G, Metcalf B. Discovery of INCB8761/PF-4136309, a Potent, Selective, and Orally Bioavailable CCR2 Antagonist. ACS Med Chem Lett. 2011 Oct 5;2(12):913-8. doi: 10.1021/ml200199c. eCollection 2011 Dec 8. PubMed PMID: 24900280; PubMed Central PMCID: PMC4018168. Zuo, Z., Hu, M., Chen, M., Chen, X., Yang, F., Zeng, C., ... & Zhang, Y. (2015). HPLC Determination of Enantiomeric Purity of PF-04136309 Based on a Chiral Stationary Phase. Chromatographia, 78, 579-583.

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