MedKoo Biosciences, Inc.
Tel:   +1-919-636-5577    Fax:   +1-919-980-4831    Email:   sales@medkoo.com
Search
Login Register
Search
MedKoo Cat#: 503216 | Name: PF-8380
Featured New

Description:

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

PF-8380 is a potent autotaxin inhibitor with an IC(50) of 2.8 nM in isolated enzyme assay and 101 nM in human whole blood. PF-8380 has adequate oral bioavailability and exposures required for in vivo testing of autotaxin inhibition. Autotaxin's role in producing LPA in plasma and at the site of inflammation was tested in a rat air pouch model. The specific inhibitor PF-8380 , dosed orally at 30 mg/kg, provided >95% reduction in both plasma and air pouch LPA within 3 h, indicating autotaxin is a major source of LPA during inflammation. At 30 mg/kg PF-8380 reduced inflammatory hyperalgesia with the same efficacy as 30 mg/kg naproxen.

Chemical Structure

PF-8380
PF-8380
CAS#1144035-53-9

Theoretical Analysis

MedKoo Cat#: 503216

Name: PF-8380

CAS#: 1144035-53-9

Chemical Formula: C22H21Cl2N3O5

Exact Mass: 477.0858

Molecular Weight: 478.33

Elemental Analysis: C, 55.24; H, 4.43; Cl, 14.82; N, 8.78; O, 16.72

Price and Availability

Size Price Availability Quantity
100mg USD 450.00 2 Weeks
200mg USD 750.00 2 Weeks
500mg USD 1,450.00 2 Weeks
1g USD 2,250.00 2 Weeks
2g USD 3,950.00 2 Weeks
5g USD 5,950.00 2 Weeks
Show More
Bulk Inquiry
Buy Now
Add to Cart
Related CAS #
No Data
Synonym
PF8380; PF-8380; PF 8380.
IUPAC/Chemical Name
3,5-dichlorobenzyl 4-(3-oxo-3-(2-oxo-2,3-dihydrobenzo[d]oxazol-6-yl)propyl)piperazine-1-carboxylate
InChi Key
JMSUDQYHPSNBSN-UHFFFAOYSA-N
InChi Code
InChI=1S/C22H21Cl2N3O5/c23-16-9-14(10-17(24)12-16)13-31-22(30)27-7-5-26(6-8-27)4-3-19(28)15-1-2-18-20(11-15)32-21(29)25-18/h1-2,9-12H,3-8,13H2,(H,25,29)
SMILES Code
O=C(N1CCN(CCC(C2=CC=C3NC(OC3=C2)=O)=O)CC1)OCC4=CC(Cl)=CC(Cl)=C4
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
>5 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
         
Product Data
Product Data
Instruction
View handling instruction
Biological target:
PF-8380 is a potent autotaxin inhibitor with an IC50 of 2.8 nM in isolated enzyme assay and 101 nM in human whole blood.
In vitro activity:
TBD
In vivo activity:
Autotaxin's role in producing LPA in plasma and at the site of inflammation was tested in a rat air pouch model. The specific inhibitor PF-8380, dosed orally at 30 mg/kg, provided >95% reduction in both plasma and air pouch LPA within 3 h, indicating autotaxin is a major source of LPA during inflammation. At 30 mg/kg PF-8380 reduced inflammatory hyperalgesia with the same efficacy as 30 mg/kg naproxen. Inhibition of plasma autotaxin activity correlated with inhibition of autotaxin at the site of inflammation and in ex vivo whole blood. Furthermore, a close pharmacokinetic/pharmacodynamic relationship was observed, which suggests that LPA is rapidly formed and degraded in vivo. Reference: J Pharmacol Exp Ther. 2010 Jul;334(1):310-7. https://pubmed.ncbi.nlm.nih.gov/20392816/
Solvent mg/mL mM comments
Solubility
DMF 5.0 10.45
DMF:PBS (pH 7.2) (1:6) 0.1 0.29
DMSO 35.2 73.64
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 478.33 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. Roy S, Chakrabarti M, Dasgupta H, Mahale A, Tripathi S, Sharma V, Banerjee M, Kulkarni OP. Inhibition of Autotaxin Ameliorates LPA-Mediated Neuroinflammation and Alleviates Neurological Dysfunction in Acute Hepatic Encephalopathy. ACS Chem Neurosci. 2022 Oct 5;13(19):2829-2841. doi: 10.1021/acschemneuro.2c00046. Epub 2022 Sep 16. PMID: 36112416. 2. Gierse J, Thorarensen A, Beltey K, Bradshaw-Pierce E, Cortes-Burgos L, Hall T, Johnston A, Murphy M, Nemirovskiy O, Ogawa S, Pegg L, Pelc M, Prinsen M, Schnute M, Wendling J, Wene S, Weinberg R, Wittwer A, Zweifel B, Masferrer J. A novel autotaxin inhibitor reduces lysophosphatidic acid levels in plasma and the site of inflammation. J Pharmacol Exp Ther. 2010 Jul;334(1):310-7. doi: 10.1124/jpet.110.165845. Epub 2010 Apr 14. PMID: 20392816.
In vitro protocol:
TBD
In vivo protocol:
1. Roy S, Chakrabarti M, Dasgupta H, Mahale A, Tripathi S, Sharma V, Banerjee M, Kulkarni OP. Inhibition of Autotaxin Ameliorates LPA-Mediated Neuroinflammation and Alleviates Neurological Dysfunction in Acute Hepatic Encephalopathy. ACS Chem Neurosci. 2022 Oct 5;13(19):2829-2841. doi: 10.1021/acschemneuro.2c00046. Epub 2022 Sep 16. PMID: 36112416. 2. Gierse J, Thorarensen A, Beltey K, Bradshaw-Pierce E, Cortes-Burgos L, Hall T, Johnston A, Murphy M, Nemirovskiy O, Ogawa S, Pegg L, Pelc M, Prinsen M, Schnute M, Wendling J, Wene S, Weinberg R, Wittwer A, Zweifel B, Masferrer J. A novel autotaxin inhibitor reduces lysophosphatidic acid levels in plasma and the site of inflammation. J Pharmacol Exp Ther. 2010 Jul;334(1):310-7. doi: 10.1124/jpet.110.165845. Epub 2010 Apr 14. PMID: 20392816.
1: Guo LZ, Tripathi H, Gao E, Tarhuni WM, Abdel-Latif A. Autotaxin Inhibition Reduces Post-Ischemic Myocardial Inflammation via Epigenetic Gene Modifications. Stem Cell Rev Rep. 2024 Jul 10. doi: 10.1007/s12015-024-10759-7. Epub ahead of print. PMID: 38985374. 2: Roy S, Chakrabarti M, Dasgupta H, Mahale A, Tripathi S, Sharma V, Banerjee M, Kulkarni OP. Inhibition of Autotaxin Ameliorates LPA-Mediated Neuroinflammation and Alleviates Neurological Dysfunction in Acute Hepatic Encephalopathy. ACS Chem Neurosci. 2022 Oct 5;13(19):2829-2841. doi: 10.1021/acschemneuro.2c00046. Epub 2022 Sep 16. PMID: 36112416. 3: Li T, Lei H, Yang J, Cao Z, Yang Y, Liu Z, Sun R, Yang X, Zhai X. Hybrid imidazo[1,2-a]pyridine analogs as potent ATX inhibitors with concrete in vivo antifibrosis effect. Arch Pharm (Weinheim). 2022 Oct;355(10):e2200171. doi: 10.1002/ardp.202200171. Epub 2022 Jun 3. PMID: 35661405. 4: Lei H, Wang X, Zhao G, Li T, Cui Y, Wu H, Yang J, Jiang N, Zhai X. Design, synthesis and promising anti-tumor efficacy of novel imidazo[1,2-a]pyridine derivatives as potent autotaxin allosteric inhibitors. Eur J Med Chem. 2022 Jun 5;236:114307. doi: 10.1016/j.ejmech.2022.114307. Epub 2022 Mar 25. PMID: 35436669. 5: Bano S, Al-Rashida M, Alharthy RD, Khan IA, Iqbal J. Nucleotide pyrophosphatase/phosphodiesterases (NPPs) including NPP1 and NPP2/ ATX as important drug targets: A patent review (2015-2020). Expert Opin Ther Pat. 2022 Jul;32(7):743-751. doi: 10.1080/13543776.2022.2058874. Epub 2022 Apr 12. PMID: 35333684. 6: Yang HL, Lai ZZ, Shi JW, Zhou WJ, Mei J, Ye JF, Zhang T, Wang J, Zhao JY, Li DJ, Li MQ. A defective lysophosphatidic acid-autophagy axis increases miscarriage risk by restricting decidual macrophage residence. Autophagy. 2022 Oct;18(10):2459-2480. doi: 10.1080/15548627.2022.2039000. Epub 2022 Feb 27. PMID: 35220880; PMCID: PMC9542369. 7: Lei H, Li Z, Li T, Wu H, Yang J, Yang X, Yang Y, Jiang N, Zhai X. Novel imidazo[1,2-a]pyridine derivatives as potent ATX allosteric inhibitors: Design, synthesis and promising in vivo anti-fibrotic efficacy in mice lung model. Bioorg Chem. 2022 Mar;120:105590. doi: 10.1016/j.bioorg.2021.105590. Epub 2021 Dec 31. PMID: 34998121. 8: Gento-Caro Á, Vilches-Herrando E, Portillo F, González-Forero D, Moreno-López B. Targeting autotaxin impacts disease advance in the SOD1-G93A mouse model of amyotrophic lateral sclerosis. Brain Pathol. 2022 May;32(3):e13022. doi: 10.1111/bpa.13022. Epub 2021 Sep 28. PMID: 34585475; PMCID: PMC9048519. 9: Joshi L, Plastira I, Bernhart E, Reicher H, Triebl A, Köfeler HC, Sattler W. Inhibition of Autotaxin and Lysophosphatidic Acid Receptor 5 Attenuates Neuroinflammation in LPS-Activated BV-2 Microglia and a Mouse Endotoxemia Model. Int J Mol Sci. 2021 Aug 7;22(16):8519. doi: 10.3390/ijms22168519. PMID: 34445223; PMCID: PMC8395174. 10: Tan Z, Lei H, Guo M, Chen Y, Zhai X. An updated patent review of autotaxin inhibitors (2017-present). Expert Opin Ther Pat. 2021 May;31(5):421-434. doi: 10.1080/13543776.2021.1867106. Epub 2021 Jan 12. PMID: 33342311. 11: Jinno N, Yoshida M, Hayashi K, Naitoh I, Hori Y, Natsume M, Kato A, Kachi K, Asano G, Atsuta N, Sahashi H, Kataoka H. Autotaxin in ascites promotes peritoneal dissemination in pancreatic cancer. Cancer Sci. 2021 Feb;112(2):668-678. doi: 10.1111/cas.14689. Epub 2020 Dec 21. PMID: 33053268; PMCID: PMC7893983. 12: Tripathi H, Al-Darraji A, Abo-Aly M, Peng H, Shokri E, Chelvarajan L, R Donahue R, Levitan BM, Gao E, Hernandez G, Morris AJ, Smyth SS, Abdel-Latif A. Autotaxin inhibition reduces cardiac inflammation and mitigates adverse cardiac remodeling after myocardial infarction. J Mol Cell Cardiol. 2020 Dec;149:95-114. doi: 10.1016/j.yjmcc.2020.09.011. Epub 2020 Oct 2. PMID: 33017574; PMCID: PMC7744112. 13: Datta P, Gandhi R, Nakamura S, Lively S, Rossomacha E, Potla P, Shestopaloff K, Endisha H, Pastrello C, Jurisica I, Rockel JS, Kapoor M. Effect of autotaxin inhibition in a surgically-induced mouse model of osteoarthritis. Osteoarthr Cartil Open. 2020 Jun 8;2(3):100080. doi: 10.1016/j.ocarto.2020.100080. PMID: 36474685; PMCID: PMC9718142. 14: Weng J, Jiang S, Ding L, Xu Y, Zhu X, Jin P. Autotaxin/lysophosphatidic acid signaling mediates obesity-related cardiomyopathy in mice and human subjects. J Cell Mol Med. 2019 Feb;23(2):1050-1058. doi: 10.1111/jcmm.14005. Epub 2018 Nov 18. PMID: 30450805; PMCID: PMC6349211. 15: Fukushima K, Otagaki S, Takahashi K, Minami K, Ishimoto K, Fukushima N, Honoki K, Tsujiuchi T. Promotion of cell-invasive activity through the induction of LPA receptor-1 in pancreatic cancer cells. J Recept Signal Transduct Res. 2018 Aug;38(4):367-371. doi: 10.1080/10799893.2018.1531889. Epub 2018 Nov 5. PMID: 30396320. 16: Ninou I, Kaffe E, Müller S, Budd DC, Stevenson CS, Ullmer C, Aidinis V. Pharmacologic targeting of the ATX/LPA axis attenuates bleomycin-induced pulmonary fibrosis. Pulm Pharmacol Ther. 2018 Oct;52:32-40. doi: 10.1016/j.pupt.2018.08.003. Epub 2018 Sep 7. PMID: 30201409. 17: He P, Haque A, Lin S, Cominelli F, Yun CC. Inhibition of autotaxin alleviates inflammation and increases the expression of sodium-dependent glucose cotransporter 1 and Na+/H+ exchanger 3 in SAMP1/Fc mice. Am J Physiol Gastrointest Liver Physiol. 2018 Nov 1;315(5):G762-G771. doi: 10.1152/ajpgi.00215.2018. Epub 2018 Aug 17. PMID: 30118349; PMCID: PMC6293258. 18: Thomson CG, Le Grand D, Dowling M, Brocklehurst CE, Chinn C, Elphick L, Faller M, Freeman M, Furminger V, Gasser C, Hamadi A, Hardaker E, Head V, Hill JC, Janus DI, Pearce D, Poulaud AS, Stanley E, Sviridenko L. Development of autotaxin inhibitors: A series of zinc binding triazoles. Bioorg Med Chem Lett. 2018 Jul 15;28(13):2279-2284. doi: 10.1016/j.bmcl.2018.05.030. Epub 2018 May 21. PMID: 29798825. 19: Kuttruff CA, Ferrara M, Bretschneider T, Hoerer S, Handschuh S, Nosse B, Romig H, Nicklin P, Roth GJ. Discovery of BI-2545: A Novel Autotaxin Inhibitor That Significantly Reduces LPA Levels in Vivo. ACS Med Chem Lett. 2017 Nov 8;8(12):1252-1257. doi: 10.1021/acsmedchemlett.7b00312. PMID: 29259743; PMCID: PMC5733304. 20: Balupuri A, Lee DY, Lee MH, Chae S, Jung E, Kim Y, Ryu J, Kang NS. Design, synthesis, docking and biological evaluation of 4-phenyl-thiazole derivatives as autotaxin (ATX) inhibitors. Bioorg Med Chem Lett. 2017 Sep 1;27(17):4156-4164. doi: 10.1016/j.bmcl.2017.07.022. Epub 2017 Jul 16. PMID: 28743508.