WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H510288
CAS#: 1341224-83-6
Description: 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.
Hodoodo Cat#: H510288
Name: PF4136309
CAS#: 1341224-83-6
Chemical Formula: C29H31F3N6O3
Exact Mass: 568.24
Molecular Weight: 568.590
Elemental Analysis: C, 61.26; H, 5.50; F, 10.02; N, 14.78; O, 8.44
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 | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 5.0 | 8.80 | |
| Ethanol | 20.0 | 35.20 |
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.
| 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.
