WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H333092
CAS#: 1144617-49-1 (free acid)
Description: Pixatimod, aslo known as PG-545, is a synthetic sugar modified heparan sulfate mimetic and agonist of toll-like receptor 9 (TLR9), with potential immunostimulating, antineoplastic and anti-viral activities. Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike-ACE2 Interaction. Pixatimod blocks a number of pro-cancerous processes including cell proliferation, invasion, metastasis, angiogenesis and epithelial-mesenchymal transition. These activities have translated into potent activity using a range of different mouse cancer models, including approximately 30 xenograft and 20 syngeneic models. Pixatimod has been tested in combination with a number of approved anti-cancer drugs demonstrating its clinical potential, including with gemcitabine, paclitaxel, sorafenib, platinum agents and an anti-PD-1 antibody.
Hodoodo Cat#: H333092
Name: Pixatimod
CAS#: 1144617-49-1 (free acid)
Chemical Formula: C51H88O60S13
Exact Mass: 2,076.02
Molecular Weight: 2,077.985
Elemental Analysis: C, 29.48; H, 4.27; O, 46.20; S, 20.06
This product is not in stock, which may be available by custom synthesis.
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Related CAS #: 1144492-69-2 (sodium) 1144617-49-1 (free acid)
Synonym: Pixatimod; PG-545; PG 545; PG545;
IUPAC/Chemical Name: (2R,3R,4S,5R,6R)-2-(((2R,3R,4S,5R,6R)-6-(((2R,3R,4S,5R,6R)-6-(((2R,3R,4S,5R,6R)-6-(((3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-((R)-6-methylheptan-2-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl)oxy)-4,5-bis(sulfooxy)-2-((sulfooxy)methyl)tetrahydro-2H-pyran-3-yl)oxy)-4,5-bis(sulfooxy)-2-((sulfooxy)methyl)tetrahydro-2H-pyran-3-yl)oxy)-4,5-bis(sulfooxy)-2-((sulfooxy)methyl)tetrahydro-2H-pyran-3-yl)oxy)-6-((sulfooxy)methyl)tetrahydro-2H-pyran-3,4,5-triyl tris(hydrogen sulfate)
InChi Key: LNUFLCYMSVYYNW-ZPJMAFJPSA-N
InChi Code: InChI=1S/C51H88O60S13/c1-22(2)7-6-8-23(3)27-11-12-28-26-10-9-24-17-25(13-15-50(24,4)29(26)14-16-51(27,28)5)95-46-42(108-121(79,80)81)38(104-117(67,68)69)34(30(96-46)18-91-112(52,53)54)100-47-43(109-122(82,83)84)39(105-118(70,71)72)35(31(97-47)19-92-113(55,56)57)101-48-44(110-123(85,86)87)40(106-119(73,74)75)36(32(98-48)20-93-114(58,59)60)102-49-45(111-124(88,89)90)41(107-120(76,77)78)37(103-116(64,65)66)33(99-49)21-94-115(61,62)63/h22-49H,6-21H2,1-5H3,(H,52,53,54)(H,55,56,57)(H,58,59,60)(H,61,62,63)(H,64,65,66)(H,67,68,69)(H,70,71,72)(H,73,74,75)(H,76,77,78)(H,79,80,81)(H,82,83,84)(H,85,86,87)(H,88,89,90)/t23-,24+,25+,26+,27-,28+,29+,30-,31-,32-,33-,34-,35-,36-,37-,38+,39+,40+,41+,42-,43-,44-,45-,46-,47-,48-,49-,50+,51-/m1/s1
SMILES Code: C[C@@]12[C@@]3([C@]([C@]4([C@](C)(CC3)[C@@]([C@@H](CCCC(C)C)C)(CC4)[H])[H])(CC[C@]1(C[C@@H](O[C@H]5[C@H](OS(=O)(=O)O)[C@@H](OS(=O)(=O)O)[C@H](O[C@@H]6[C@H](OS(=O)(=O)O)[C@@H](OS(=O)(=O)O)[C@H](O[C@@H]7[C@H](OS(=O)(=O)O)[C@@H](OS(=O)(=O)O)[C@H](O[C@@H]8[C@H](OS(=O)(=O)O)[C@@H](OS(=O)(=O)O)[C@H](OS(=O)(=O)O)[C@@H](COS(=O)(=O)O)O8)[C@@H](COS(=O)(=O)O)O7)[C@@H](COS(=O)(=O)O)O6)[C@@H](COS(=O)(=O)O)O5)CC2)[H])[H])[H]
Appearance: To be determined
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: To be determined
Shelf Life: >2 years if stored properly
Drug Formulation: To be determined
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: TLR9, a member of the TLR family, plays a fundamental role in pathogen recognition and activation of innate immunity. Heparan sulfate (HS) is a cell surface polysaccharide recently identified as a coreceptor with the ACE2 protein for the S1 spike protein on SARS-CoV-2 virus, providing a tractable new therapeutic target. Clinically used heparins demonstrate an inhibitory activity but have an anticoagulant activity and are supply-limited, necessitating alternative solutions
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The following data is based on the product molecular weight 2,077.99 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: | |
| In vitro protocol: | |
| In vivo protocol: |
1: Lemech C, Dredge K, Bampton D, Hammond E, Clouston A, Waterhouse NJ, Stanley AC, Leveque-El Mouttie L, Chojnowski GM, Haydon A, Pavlakis N, Burge M, Brown MP, Goldstein D. Phase Ib open-label, multicenter study of pixatimod, an activator of TLR9, in combination with nivolumab in subjects with microsatellite-stable metastatic colorectal cancer, metastatic pancreatic ductal adenocarcinoma and other solid tumors. J Immunother Cancer. 2023 Jan;11(1):e006136. doi: 10.1136/jitc-2022-006136. PMID: 36634920; PMCID: PMC9843174.
2: Guimond SE, Mycroft-West CJ, Gandhi NS, Tree JA, Le TT, Spalluto CM, Humbert MV, Buttigieg KR, Coombes N, Elmore MJ, Wand M, Nyström K, Said J, Setoh YX, Amarilla AA, Modhiran N, Sng JDJ, Chhabra M, Young PR, Rawle DJ, Lima MA, Yates EA, Karlsson R, Miller RL, Chen YH, Bagdonaite I, Yang Z, Stewart J, Nguyen D, Laidlaw S, Hammond E, Dredge K, Wilkinson TMA, Watterson D, Khromykh AA, Suhrbier A, Carroll MW, Trybala E, Bergström T, Ferro V, Skidmore MA, Turnbull JE. Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS- CoV-2 by Disrupting the Spike-ACE2 Interaction. ACS Cent Sci. 2022 May 25;8(5):527-545. doi: 10.1021/acscentsci.1c01293. Epub 2022 Mar 29. PMID: 35647275; PMCID: PMC9136977.
3: Chhabra M, Wilson JC, Wu L, Davies GJ, Gandhi NS, Ferro V. Structural Insights into Pixatimod (PG545) Inhibition of Heparanase, a Key Enzyme in Cancer and Viral Infections. Chemistry. 2022 Feb 19;28(11):e202104222. doi: 10.1002/chem.202104222. Epub 2022 Jan 31. PMID: 34981584; PMCID: PMC9303737.
4: Chhabra M, Wimmer N, He QQ, Ferro V. Development of Improved Synthetic Routes to Pixatimod (PG545), a Sulfated Oligosaccharide-Steroid Conjugate. Bioconjug Chem. 2021 Nov 17;32(11):2420-2431. doi: 10.1021/acs.bioconjchem.1c00453. Epub 2021 Oct 15. PMID: 34652896.
5: Kinaneh S, Khamaysi I, Karram T, Hamoud S. Heparanase as a potential player in SARS-CoV-2 infection and induced coagulopathy. Biosci Rep. 2021 Jul 30;41(7):BSR20210290. doi: 10.1042/BSR20210290. PMID: 34132790; PMCID: PMC8255537.
6: Hammond E, Dredge K. Heparanase Inhibition by Pixatimod (PG545): Basic Aspects and Future Perspectives. Adv Exp Med Biol. 2020;1221:539-565. doi: 10.1007/978-3-030-34521-1_22. PMID: 32274726.
7: Chhabra M, Ferro V. PI-88 and Related Heparan Sulfate Mimetics. Adv Exp Med Biol. 2020;1221:473-491. doi: 10.1007/978-3-030-34521-1_19. PMID: 32274723.
8: Bendersky V, Yang Y, Brennan TV. Immunomodulatory Activities of the Heparan Sulfate Mimetic PG545. Adv Exp Med Biol. 2020;1221:461-470. doi: 10.1007/978-3-030-34521-1_18. PMID: 32274722.
9: Koliesnik IO, Kuipers HF, Medina CO, Zihsler S, Liu D, Van Belleghem JD, Bollyky PL. The Heparan Sulfate Mimetic PG545 Modulates T Cell Responses and Prevents Delayed-Type Hypersensitivity. Front Immunol. 2020 Feb 6;11:132. doi: 10.3389/fimmu.2020.00132. PMID: 32117279; PMCID: PMC7015948.
10: Hammond E, Haynes NM, Cullinane C, Brennan TV, Bampton D, Handley P, Karoli T, Lanksheer F, Lin L, Yang Y, Dredge K. Immunomodulatory activities of pixatimod: emerging nonclinical and clinical data, and its potential utility in combination with PD-1 inhibitors. J Immunother Cancer. 2018 Jun 14;6(1):54. doi: 10.1186/s40425-018-0363-5. PMID: 29898788; PMCID: PMC6000956.
11: Dredge K, Brennan TV, Hammond E, Lickliter JD, Lin L, Bampton D, Handley P, Lankesheer F, Morrish G, Yang Y, Brown MP, Millward M. A Phase I study of the novel immunomodulatory agent PG545 (pixatimod) in subjects with advanced solid tumours. Br J Cancer. 2018 Apr;118(8):1035-1041. doi: 10.1038/s41416-018-0006-0. Epub 2018 Mar 13. PMID: 29531325; PMCID: PMC5931096.
