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. PF-05231023 significantly reduced body weight, hepatomegaly, plasma transaminases, and plasma/liver lipids in GAN DIO-NASH mice. Notably, PF-05231023 reduced both NAS (≥2-point improvement) and fibrosis stage (1-point improvement). Improvements in NASH and fibrosis severity were supported by reduced quantitative histological markers of steatosis, inflammation, and fibrogenesis as well as improvements in disease-associated liver transcriptome signatures.

Chemical Structure

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PF-05231023
CAS# 1037589-69-7
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 530533
Name: PF-05231023
CAS#: 1037589-69-7
Chemical Formula: C26H32N4O8
Exact Mass: 528.22
Molecular Weight: 528.560
Elemental Analysis: C, 59.08; H, 6.10; N, 10.60; O, 24.22

Price and Availability

Size Price Availability Quantity
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1250 Ready to ship
500mg USD 2850 Ready to ship
1g USD 4250 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

More Info: Fibroblast growth factor 21 (FGF21) plays a key role in hepatic lipid metabolism and long-acting FGF21 analogs have emerged as promising drug candidates for the treatment of nonalcoholic steatohepatitis (NASH). It remains to characterize this drug class in translational animal models that recapitulate the etiology and hallmarks of human disease

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: Ho MF, Zhang C, Moon I, Biernacka J, Coombes B, Ngo Q, Skillon C, Skime M, Oesterle T, Croarkin PE, Karpyak VM, Li H, Weinshilboum RM. Epigenetic regulation of GABA catabolism in iPSC-derived neurons: The molecular links between FGF21 and histone methylation. Mol Metab. 2023 Nov;77:101798. doi: 10.1016/j.molmet.2023.101798. Epub 2023 Sep 7. PMID: 37689244; PMCID: PMC10514449.


2: Mi XX, Yan J, Shi JP. [Improvement situation on indexes of the zebrafish disease model of non-alcoholic fatty liver disease with FGF21 analogues]. Zhonghua Gan Zang Bing Za Zhi. 2023 Jul 20;31(7):742-749. Chinese. doi: 10.3760/cma.j.cn501113-20230103-00002. PMID: 37580258.


3: Nielsen MH, Gillum MP, Vrang N, Jelsing J, Hansen HH, Feigh M, Oró D. Hepatoprotective effects of the long-acting fibroblast growth factor 21 analog PF-05231023 in the GAN diet-induced obese and biopsy-confirmed mouse model of nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol. 2023 May 1;324(5):G378-G388. doi: 10.1152/ajpgi.00157.2022. Epub 2023 Feb 28. PMID: 36852934.


4: Flippo KH, Trammell SAJ, Gillum MP, Aklan I, Perez MB, Yavuz Y, Smith NK, Jensen-Cody SO, Zhou B, Claflin KE, Beierschmitt A, Fink-Jensen A, Knop FK, Palmour RM, Grueter BA, Atasoy D, Potthoff MJ. FGF21 suppresses alcohol consumption through an amygdalo-striatal circuit. Cell Metab. 2022 Feb 1;34(2):317-328.e6. doi: 10.1016/j.cmet.2021.12.024. PMID: 35108517; PMCID: PMC9093612.


5: Xie T, So WY, Li XY, Leung PS. Fibroblast growth factor 21 protects against lipotoxicity-induced pancreatic β-cell dysfunction via regulation of AMPK signaling and lipid metabolism. Clin Sci (Lond). 2019 Oct 15;133(19):2029-2044. doi: 10.1042/CS20190093. PMID: 31654570.


6: Struik D, Dommerholt MB, Jonker JW. Fibroblast growth factors in control of lipid metabolism: from biological function to clinical application. Curr Opin Lipidol. 2019 Jun;30(3):235-243. doi: 10.1097/MOL.0000000000000599. PMID: 30893110; PMCID: PMC6530965.


7: Turner T, Chen X, Zahner M, Opsahl A, DeMarco G, Boucher M, Goodwin B, Perreault M. FGF21 increases water intake, urine output and blood pressure in rats. PLoS One. 2018 Aug 14;13(8):e0202182. doi: 10.1371/journal.pone.0202182. PMID: 30106981; PMCID: PMC6091943.


8: Weng Y, Ishino T, Sievers A, Talukdar S, Chabot JR, Tam A, Duan W, Kerns K, Sousa E, He T, Logan A, Lee D, Li D, Zhou Y, Bernardo B, Joyce A, Kavosi M, O'Hara DM, Clark T, Guo J, Giragossian C, Stahl M, Calle RA, Kriz R, Somers W, Lin L. Glyco-engineered Long Acting FGF21 Variant with Optimal Pharmaceutical and Pharmacokinetic Properties to Enable Weekly to Twice Monthly Subcutaneous Dosing. Sci Rep. 2018 Mar 9;8(1):4241. doi: 10.1038/s41598-018-22456-w. PMID: 29523796; PMCID: PMC5844872.


9: 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.


10: Kim AM, Somayaji VR, Dong JQ, Rolph TP, Weng Y, Chabot JR, Gropp KE, Talukdar S, Calle RA. Once-weekly administration of a long-acting fibroblast growth factor 21 analogue modulates lipids, bone turnover markers, blood pressure and body weight differently in obese people with hypertriglyceridaemia and in non-human primates. Diabetes Obes Metab. 2017 Dec;19(12):1762-1772. doi: 10.1111/dom.13023. Epub 2017 Jul 21. PMID: 28573777.


11: 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. Epub 2016 Jul 12. PMID: 27405817; PMCID: PMC4954843.


12: 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. PMID: 26959184.


13: 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. PMID: 26153793; PMCID: PMC4495598.


14: 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. Epub 2015 Jul 29. PMID: 25940675; PMCID: PMC4631178.


15: 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.


16: 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. PMID: 25790234; PMCID: PMC4366384.

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