PF-05231023
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MedKoo CAT#: 530533

CAS#: 1037589-69-7

Description: PF-05231023 is a long-acting FGF21 mimetic. PF-05231023 decreases body weight and improves lipid profile in non-human primates and in type 2 diabetic subjects.


Chemical Structure

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PF-05231023
CAS# 1037589-69-7

Theoretical Analysis

MedKoo Cat#: 530533
Name: PF-05231023
CAS#: 1037589-69-7
Chemical Formula: C26H32N4O8
Exact Mass: 528.222
Molecular Weight: 528.56
Elemental Analysis: C, 59.08; H, 6.10; N, 10.60; O, 24.22

Price and Availability

Size Price Availability Quantity
10.0mg USD 150.0 Ready to ship
25.0mg USD 250.0 Ready to ship
50.0mg USD 450.0 Ready to ship
100.0mg USD 750.0 Ready to ship
200.0mg USD 1250.0 Ready to ship
500.0mg USD 2850.0 Ready to ship
1.0g USD 4250.0 Ready to ship
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Synonym: PF-05231023; PF05231023; PF 05231023; PF-5231023; PF5231023; PF 5231023

IUPAC/Chemical Name: 2,5-Dihydro-2,5-dioxo-N-[2-[2-[3-oxo-3-[[4-[3-oxo-3-(2-oxo-1-azetidinyl)propyl]phenyl]amino]propoxy]ethoxy]ethyl]-1H-pyrrole-1-propanamide

InChi Key: BJDLYWUPKGDHCF-UHFFFAOYSA-N

InChi Code: InChI=1S/C26H32N4O8/c31-21(9-13-29-24(34)7-8-25(29)35)27-12-16-38-18-17-37-15-11-22(32)28-20-4-1-19(2-5-20)3-6-23(33)30-14-10-26(30)36/h1-2,4-5,7-8H,3,6,9-18H2,(H,27,31)(H,28,32)

SMILES Code: O=C(NCCOCCOCCC(NC1=CC=C(CCC(N2C(CC2)=O)=O)C=C1)=O)CCN3C(C=CC3=O)=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

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

Biological target: PF-05231023, a long-acting fibroblast growth factor 21 (FGF21) analog, is a FGF21-receptor agonist, suitable for development as a potential treatment for T2DM.
In vitro activity: PF-05231023, a long-acting fibroblast growth factor 21 (FGF21) analog, was generated by covalently conjugating two engineered [des-His1, Ala129Cys]FGF21 molecules to a nontargeting human IgG1 κ scaffold. In vitro serum stability studies in monkeys and humans suggested that the principal CL mechanism for PF-05231023 was degradation by serum proteases. Mechanistic physiologically based pharmacokinetic models of this nature may be highly valuable for predicting human PK of fusion proteins, synthetically conjugated proteins, and other complex biologics. Reference: Drug Metab Dispos. 2015 Jun;43(6):803-11. https://pubmed.ncbi.nlm.nih.gov/25805881/
In vivo activity: To test whether APN mediated the protective effects of PF-05231023, diabetes was induced with an injection of STZ in 6- to 8-weekold WT and Apn−/− mice. Retinal function was then examined by ERG at 7–8 months of age. Again, PF-05231023 administration did not change body weight, blood glucose levels, or serum triglyceride levels (Supplementary Fig. 5). Furthermore, neither the amplitude nor sensitivity of the a-wave, b-wave, or the OPs differed significantly between STZ-treated mice (Fig. 6A–C), but Sm was significantly attenuated after STZ treatment (F = 12.2, df = 1,6.0, P = 0.013) (Fig. 6D). PF-05231023, administered as described above, again improved log Sm values (F = 45.2, df = 1,5.9, P = 0.001) in the STZ-treated mice to levels that were supranormal (Fig. 6D and E). The protective effects of PF-05231023 on retinal sensitivity (log Sm) in STZ-induced WT diabetic mice were again found in Apn−/− diabetic mice (F = 23.8, df = 1,2, P = 0.040) (Fig. 6F–H), suggesting that the rescue was partly independent of APN. In the STZ-induced diabetic mice, PF-05231023 decreased IL-1β expression in diabetic WT and Apn−/− retinas (Fig. 6I), suggesting that PF-05231023–induced reduction in IL-1β was independent of APN Reference: Diabetes. 2018 May; 67(5): 974–985. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5909994/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 125.0 236.49

Preparing Stock Solutions

The following data is based on the product molecular weight 528.56 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. Giragossian C, Vage C, Li J, Pelletier K, Piché-Nicholas N, Rajadhyaksha M, Liras J, Logan A, Calle RA, Weng Y. Mechanistic investigation of the preclinical pharmacokinetics and interspecies scaling of PF-05231023, a fibroblast growth factor 21-antibody protein conjugate. Drug Metab Dispos. 2015 Jun;43(6):803-11. doi: 10.1124/dmd.114.061713. Epub 2015 Mar 24. PMID: 25805881 2. Fu Z, Wang Z, Liu CH, Gong Y, Cakir B, Liegl R, Sun Y, Meng SS, Burnim SB, Arellano I, Moran E, Duran R, Poblete A, Cho SS, Talukdar S, Akula JD, Hellström A, Smith LEH. Fibroblast Growth Factor 21 Protects Photoreceptor Function in Type 1 Diabetic Mice. Diabetes. 2018 May;67(5):974-985. doi: 10.2337/db17-0830. Epub 2018 Feb 27. PMID: 29487115; PMCID: PMC5909994. 3. Thompson WC, Zhou Y, Talukdar S, Musante CJ. PF-05231023, a long-acting FGF21 analogue, decreases body weight by reduction of food intake in non-human primates. J Pharmacokinet Pharmacodyn. 2016 Aug;43(4):411-25. doi: 10.1007/s10928-0169481-1. Epub 2016 Jul 12. PMID: 27405817; PMCID: PMC4954843.
In vitro protocol: 1. Giragossian C, Vage C, Li J, Pelletier K, Piché-Nicholas N, Rajadhyaksha M, Liras J, Logan A, Calle RA, Weng Y. Mechanistic investigation of the preclinical pharmacokinetics and interspecies scaling of PF-05231023, a fibroblast growth factor 21-antibody protein conjugate. Drug Metab Dispos. 2015 Jun;43(6):803-11. doi: 10.1124/dmd.114.061713. Epub 2015 Mar 24. PMID: 25805881.
In vivo protocol: 1. Fu Z, Wang Z, Liu CH, Gong Y, Cakir B, Liegl R, Sun Y, Meng SS, Burnim SB, Arellano I, Moran E, Duran R, Poblete A, Cho SS, Talukdar S, Akula JD, Hellström A, Smith LEH. Fibroblast Growth Factor 21 Protects Photoreceptor Function in Type 1 Diabetic Mice. Diabetes. 2018 May;67(5):974-985. doi: 10.2337/db17-0830. Epub 2018 Feb 27. PMID: 29487115; PMCID: PMC5909994. 2. Thompson WC, Zhou Y, Talukdar S, Musante CJ. PF-05231023, a long-acting FGF21 analogue, decreases body weight by reduction of food intake in non-human primates. J Pharmacokinet Pharmacodyn. 2016 Aug;43(4):411-25. doi: 10.1007/s10928-0169481-1. Epub 2016 Jul 12. PMID: 27405817; PMCID: PMC4954843

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1: Talukdar S, Zhou Y, Li D, Rossulek M, Dong J, Somayaji V, Weng Y, Clark R, Lanba A, Owen BM, Brenner MB, Trimmer JK, Gropp KE, Chabot JR, Erion DM, Rolph TP, Goodwin B, Calle RA. A Long-Acting FGF21 Molecule, PF-05231023, Decreases Body Weight and Improves Lipid Profile in Non-human Primates and Type 2 Diabetic Subjects. Cell Metab. 2016 Mar 8;23(3):427-40. doi: 10.1016/j.cmet.2016.02.001. PubMed PMID: 26959184.

2: Dong JQ, Rossulek M, Somayaji VR, Baltrukonis D, Liang Y, Hudson K, Hernandez-Illas M, Calle RA. Pharmacokinetics and pharmacodynamics of PF-05231023, a novel long-acting FGF21 mimetic, in a first-in-human study. Br J Clin Pharmacol. 2015 Nov;80(5):1051-63. doi: 10.1111/bcp.12676. PubMed PMID: 25940675; PubMed Central PMCID: PMC4631178.

3: Giragossian C, Vage C, Li J, Pelletier K, Piché-Nicholas N, Rajadhyaksha M, Liras J, Logan A, Calle RA, Weng Y. Mechanistic investigation of the preclinical pharmacokinetics and interspecies scaling of PF-05231023, a fibroblast growth factor 21-antibody protein conjugate. Drug Metab Dispos. 2015 Jun;43(6):803-11. doi: 10.1124/dmd.114.061713. PubMed PMID: 25805881.

4: Weng Y, Chabot JR, Bernardo B, Yan Q, Zhu Y, Brenner MB, Vage C, Logan A, Calle R, Talukdar S. Pharmacokinetics (PK), pharmacodynamics (PD) and integrated PK/PD modeling of a novel long acting FGF21 clinical candidate PF-05231023 in diet-induced obese and leptin-deficient obese mice. PLoS One. 2015 Mar 19;10(3):e0119104. doi: 10.1371/journal.pone.0119104. PubMed PMID: 25790234; PubMed Central PMCID: PMC4366384.

5: Thompson WC, Zhou Y, Talukdar S, Musante CJ. PF-05231023, a long-acting FGF21 analogue, decreases body weight by reduction of food intake in non-human primates. J Pharmacokinet Pharmacodyn. 2016 Aug;43(4):411-25. doi: 10.1007/s10928-016-9481-1. PubMed PMID: 27405817; PubMed Central PMCID: PMC4954843.

6: Bernardo B, Lu M, Bandyopadhyay G, Li P, Zhou Y, Huang J, Levin N, Tomas EM, Calle RA, Erion DM, Rolph TP, Brenner M, Talukdar S. FGF21 does not require interscapular brown adipose tissue and improves liver metabolic profile in animal models of obesity and insulin-resistance. Sci Rep. 2015 Jul 8;5:11382. doi: 10.1038/srep11382. PubMed PMID: 26153793; PubMed Central PMCID: PMC4495598.