Saridegib free base | CAS#1037210-93-7 | Hedgehog inhibitor

MedKoo Cat#: 201572 | Name: Saridegib free base

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Description:

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

Saridegib, also known as Patidegip and IPI-926, is an orally bioavailable, cyclopamine-derived inhibitor of the Hedgehog (Hh) pathway with potential antineoplastic activity. Saridegib binds to and inhibits the cell membrane-spanning G-protein coupled receptor SMO, which may result in the suppression of Hh pathway signaling and a decrease in tumor cell proliferation and survival.

Chemical Structure

Saridegib free base

CAS#1037210-93-7 (free base)

Theoretical Analysis

MedKoo Cat#: 201572

Name: Saridegib free base

CAS#: 1037210-93-7 (free base)

Chemical Formula: C29H48N2O3S

Exact Mass: 504.3386

Molecular Weight: 504.77

Elemental Analysis: C, 69.00; H, 9.58; N, 5.55; O, 9.51; S, 6.35

Price and Availability

Size	Price	Availability
2mg	USD 950.00	2 Weeks
5mg	USD 1,650.00	2 Weeks
10mg	USD 2,950.00	2 Weeks

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Related CAS #

1037210-93-7 (free base) 1169829-40-6 (HCl)

Synonym

IPI 926; IPI-926; IPI926; Saridegib; Patidegip; Patidegib Free Base; WHO9619; WHO-9619; WHO 9619

IUPAC/Chemical Name

N-((2S,3R,3aS,3'R,4a'R,6S,6a'R,6b'S,7aR,12a'S,12b'S)-3,6,11',12b'-tetramethyl-2',3a,3',4,4',4a',5,5',6,6',6a',6b',7,7a,7',8',10',12',12a',12b'-icosahydro-1'H,3H-spiro[furo[3,2-b]pyridine-2,9'-naphtho[2,1-a]azulen]-3'-yl)methanesulfonamide

InChi Key

HZLFFNCLTRVYJG-WWGOJCOQSA-N

InChi Code

InChI=1S/C29H48N2O3S/c1-17-12-26-27(30-16-17)19(3)29(34-26)11-9-22-23-7-6-20-13-21(31-35(5,32)33)8-10-28(20,4)25(23)14-24(22)18(2)15-29/h17,19-23,25-27,30-31H,6-16H2,1-5H3/t17-,19+,20+,21+,22-,23-,25-,26+,27-,28-,29-/m0/s1

SMILES Code

CS(=O)(N[C@H](CC[C@@]12C)C[C@@]1([H])CC[C@]3([H])[C@]2([H])CC4=C(C)C[C@@](O5)(CC[C@@]34[H])[C@H](C)[C@@]6([H])[C@@]5([H])C[C@H](C)CN6)=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

Fig 1. Chemical structure comparison between IPI-926 and cyclopamine IPI-926 is currently developed by Infinity Pharmaceuticals, Inc. Malignant activation of the Hedgehog pathway is implicated in multiple cancer settings and Infinity's development strategy is designed to enable IPI-926 to target a broad range of critical oncology targets - from the tumor cell to the cancer microenvironment. This broadly applicable, targeted approach represents an innovative method for fighting cancer and has potential in treating a range of cancers, including pancreatic cancer, small cell lung cancer, ovarian cancer, bladder cancer, medulloblastoma, basal cell carcinoma, and certain hematological malignancies.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot# C21M10G14

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Saridegib is a potent and specific Smo inhibitor.

In vitro activity:

Saridegib potential therapeutic agent for human B-cell acute lymphocytic leukemia (B-ALL). The expression of Hh pathway components was common in B-ALL cell lines and clinical samples. Saridegib modulated Hh pathway activity in B-ALL cells. The primary impact of inhibiting this pathway activity was on highly clonogenic B-ALL cells that expressed aldehyde dehydrogenase (ALDH), limiting their self-renewal potential. Reference: PLoS One. 2010 Dec 28;5(12):e15262. https://pubmed.ncbi.nlm.nih.gov/21203400/

In vivo activity:

This study evaluated saridegib in combination with FOLFIRINOX in patients with advanced pancreatic cancer. The objective response rate was high (67%), and patients receiving saridegib maintenance showed further declines in CA19-9 levels even after FOLFIRINOX discontinuation. Treatment did not result in consistent increases in tumor perfusion. This study closed early when a separate phase II trial of saridegib plus gemcitabine indicated detrimental effects of this combination. Reference: Pancreas. 2016 Mar;45(3):370-5. https://pubmed.ncbi.nlm.nih.gov/26390428/

	Solvent	mg/mL	mM
Solubility
	DMSO	10.0	19.81

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 504.77 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. Ma H, Tian Y, Yu X. Targeting Smoothened Sensitizes Gastric Cancer to Chemotherapy in Experimental Models. Med Sci Monit. 2017 Mar 28;23:1493-1500. doi: 10.12659/msm.903012. PMID: 28350784; PMCID: PMC5381338. 2. Lin TL, Wang QH, Brown P, Peacock C, Merchant AA, Brennan S, Jones E, McGovern K, Watkins DN, Sakamoto KM, Matsui W. Self-renewal of acute lymphocytic leukemia cells is limited by the Hedgehog pathway inhibitors cyclopamine and IPI-926. PLoS One. 2010 Dec 28;5(12):e15262. doi: 10.1371/journal.pone.0015262. PMID: 21203400; PMCID: PMC3011010. 3. Ko AH, LoConte N, Tempero MA, Walker EJ, Kate Kelley R, Lewis S, Chang WC, Kantoff E, Vannier MW, Catenacci DV, Venook AP, Kindler HL. A Phase I Study of FOLFIRINOX Plus IPI-926, a Hedgehog Pathway Inhibitor, for Advanced Pancreatic Adenocarcinoma. Pancreas. 2016 Mar;45(3):370-5. doi: 10.1097/MPA.0000000000000458. PMID: 26390428; PMCID: PMC5908466. 4. Bowles DW, Keysar SB, Eagles JR, Wang G, Glogowska MJ, McDermott JD, Le PN, Gao D, Ray CE, Rochon PJ, Roop DR, Tan AC, Serracino HS, Jimeno A. A pilot study of cetuximab and the hedgehog inhibitor IPI-926 in recurrent/metastatic head and neck squamous cell carcinoma. Oral Oncol. 2016 Feb;53:74-9. doi: 10.1016/j.oraloncology.2015.11.014. Epub 2015 Dec 15. PMID: 26705064; PMCID: PMC5676309.

In vitro protocol:

In vivo protocol:

1. Ko AH, LoConte N, Tempero MA, Walker EJ, Kate Kelley R, Lewis S, Chang WC, Kantoff E, Vannier MW, Catenacci DV, Venook AP, Kindler HL. A Phase I Study of FOLFIRINOX Plus IPI-926, a Hedgehog Pathway Inhibitor, for Advanced Pancreatic Adenocarcinoma. Pancreas. 2016 Mar;45(3):370-5. doi: 10.1097/MPA.0000000000000458. PMID: 26390428; PMCID: PMC5908466. 2. Bowles DW, Keysar SB, Eagles JR, Wang G, Glogowska MJ, McDermott JD, Le PN, Gao D, Ray CE, Rochon PJ, Roop DR, Tan AC, Serracino HS, Jimeno A. A pilot study of cetuximab and the hedgehog inhibitor IPI-926 in recurrent/metastatic head and neck squamous cell carcinoma. Oral Oncol. 2016 Feb;53:74-9. doi: 10.1016/j.oraloncology.2015.11.014. Epub 2015 Dec 15. PMID: 26705064; PMCID: PMC5676309.

1: Montori M, Scorzoni C, Argenziano ME, Balducci D, De Blasio F, Martini F, Buono T, Benedetti A, Marzioni M, Maroni L. Cancer-Associated Fibroblasts in Cholangiocarcinoma: Current Knowledge and Possible Implications for Therapy. J Clin Med. 2022 Nov 2;11(21):6498. doi: 10.3390/jcm11216498. PMID: 36362726; PMCID: PMC9654416. 2: Cosio T, Di Prete M, Di Raimondo C, Garofalo V, Lozzi F, Lanna C, Dika E, Orlandi A, Rapanotti MC, Bianchi L, Campione E. Patidegib in Dermatology: A Current Review. Int J Mol Sci. 2021 Oct 3;22(19):10725. doi: 10.3390/ijms221910725. PMID: 34639065; PMCID: PMC8509734. 3: Neelakantan D, Zhou H, Oliphant MUJ, Zhang X, Simon LM, Henke DM, Shaw CA, Wu MF, Hilsenbeck SG, White LD, Lewis MT, Ford HL. EMT cells increase breast cancer metastasis via paracrine GLI activation in neighbouring tumour cells. Nat Commun. 2017 Jun 12;8:15773. doi: 10.1038/ncomms15773. Erratum in: Nat Commun. 2018 Nov 12;9(1):4720. doi: 10.1038/s41467-018-07168-z. PMID: 28604738; PMCID: PMC5472791. 4: Ma H, Tian Y, Yu X. Targeting Smoothened Sensitizes Gastric Cancer to Chemotherapy in Experimental Models. Med Sci Monit. 2017 Mar 28;23:1493-1500. doi: 10.12659/msm.903012. PMID: 28350784; PMCID: PMC5381338. 5: Lauressergues E, Heusler P, Lestienne F, Troulier D, Rauly-Lestienne I, Tourette A, Ailhaud MC, Cathala C, Tardif S, Denais-Laliève D, Calmettes MT, Degryse AD, Dumoulin A, De Vries L, Cussac D. Pharmacological evaluation of a series of smoothened antagonists in signaling pathways and after topical application in a depilated mouse model. Pharmacol Res Perspect. 2016 Mar 4;4(2):e00214. doi: 10.1002/prp2.214. PMID: 27069629; PMCID: PMC4804317. 6: Bowles DW, Keysar SB, Eagles JR, Wang G, Glogowska MJ, McDermott JD, Le PN, Gao D, Ray CE, Rochon PJ, Roop DR, Tan AC, Serracino HS, Jimeno A. A pilot study of cetuximab and the hedgehog inhibitor IPI-926 in recurrent/metastatic head and neck squamous cell carcinoma. Oral Oncol. 2016 Feb;53:74-9. doi: 10.1016/j.oraloncology.2015.11.014. Epub 2015 Dec 15. PMID: 26705064; PMCID: PMC5676309. 7: Ko AH, LoConte N, Tempero MA, Walker EJ, Kate Kelley R, Lewis S, Chang WC, Kantoff E, Vannier MW, Catenacci DV, Venook AP, Kindler HL. A Phase I Study of FOLFIRINOX Plus IPI-926, a Hedgehog Pathway Inhibitor, for Advanced Pancreatic Adenocarcinoma. Pancreas. 2016 Mar;45(3):370-5. doi: 10.1097/MPA.0000000000000458. PMID: 26390428; PMCID: PMC5908466. 8: Lim Y, Gondek L, Li L, Wang Q, Ma H, Chang E, Huso DL, Foerster S, Marchionni L, McGovern K, Watkins DN, Peacock CD, Levis M, Smith BD, Merchant AA, Small D, Matsui W. Integration of Hedgehog and mutant FLT3 signaling in myeloid leukemia. Sci Transl Med. 2015 Jun 10;7(291):291ra96. doi: 10.1126/scitranslmed.aaa5731. Erratum in: Sci Transl Med. 2015 Jul 8;7(295):295er6. doi: 10.1126/scitranslmed.aac9303. Ma, Haley [corrected to Ma, Hayley]. PMID: 26062848; PMCID: PMC4644635. 9: Akare UR, Bandaru S, Shaheen U, Singh PK, Tiwari G, Singare P, Nayarisseri A, Banerjee T. Molecular docking approaches in identification of High affinity inhibitors of Human SMO receptor. Bioinformation. 2014 Dec 31;10(12):737-42. doi: 10.6026/97320630010737. PMID: 25670876; PMCID: PMC4312366. 10: Justilien V, Fields AP. Molecular pathways: novel approaches for improved therapeutic targeting of Hedgehog signaling in cancer stem cells. Clin Cancer Res. 2015 Feb 1;21(3):505-13. doi: 10.1158/1078-0432.CCR-14-0507. PMID: 25646180; PMCID: PMC4316382. 11: Sasaki K, Gotlib JR, Mesa RA, Newberry KJ, Ravandi F, Cortes JE, Kelly P, Kutok JL, Kantarjian HM, Verstovsek S. Phase II evaluation of IPI-926, an oral Hedgehog inhibitor, in patients with myelofibrosis. Leuk Lymphoma. 2015 Jul;56(7):2092-7. doi: 10.3109/10428194.2014.984703. Epub 2015 Feb 17. PMID: 25641433; PMCID: PMC4919663. 12: Zhu GA, Li AS, Chang AL. Patient with Gorlin syndrome and metastatic basal cell carcinoma refractory to smoothened inhibitors. JAMA Dermatol. 2014 Aug;150(8):877-9. doi: 10.1001/jamadermatol.2013.8744. PMID: 24898076. 13: Campbell VT, Nadesan P, Ali SA, Wang CY, Whetstone H, Poon R, Wei Q, Keilty J, Proctor J, Wang LW, Apte SS, McGovern K, Alman BA, Wunder JS. Hedgehog pathway inhibition in chondrosarcoma using the smoothened inhibitor IPI-926 directly inhibits sarcoma cell growth. Mol Cancer Ther. 2014 May;13(5):1259-69. doi: 10.1158/1535-7163.MCT-13-0731. Epub 2014 Mar 14. PMID: 24634412. 14: Peluso MO, Campbell VT, Harari JA, Tibbitts TT, Proctor JL, Whitebread N, Conley JM, White KF, Kutok JL, Read MA, McGovern K, Faia KL. Impact of the Smoothened inhibitor, IPI-926, on smoothened ciliary localization and Hedgehog pathway activity. PLoS One. 2014 Mar 7;9(3):e90534. doi: 10.1371/journal.pone.0090534. PMID: 24608250; PMCID: PMC3946503. 15: Lo WW, Wunder JS, Dickson BC, Campbell V, McGovern K, Alman BA, Andrulis IL. Involvement and targeted intervention of dysregulated Hedgehog signaling in osteosarcoma. Cancer. 2014 Feb 15;120(4):537-47. doi: 10.1002/cncr.28439. Epub 2013 Oct 21. PMID: 24151134. 16: Ma H, Li HQ, Zhang X. Cyclopamine, a naturally occurring alkaloid, and its analogues may find wide applications in cancer therapy. Curr Top Med Chem. 2013;13(17):2208-15. doi: 10.2174/15680266113139990153. PMID: 23978132. 17: Sandhiya S, Melvin G, Kumar SS, Dkhar SA. The dawn of hedgehog inhibitors: Vismodegib. J Pharmacol Pharmacother. 2013 Jan;4(1):4-7. doi: 10.4103/0976-500X.107628. PMID: 23662017; PMCID: PMC3643342. 18: Keysar SB, Le PN, Anderson RT, Morton JJ, Bowles DW, Paylor JJ, Vogler BW, Thorburn J, Fernandez P, Glogowska MJ, Takimoto SM, Sehrt DB, Gan GN, Eagles- Soukup JR, Serracino H, Hirsch FR, Lucia MS, Thorburn A, Song JI, Wang XJ, Jimeno A. Hedgehog signaling alters reliance on EGF receptor signaling and mediates anti-EGFR therapeutic resistance in head and neck cancer. Cancer Res. 2013 Jun 1;73(11):3381-92. doi: 10.1158/0008-5472.CAN-12-4047. Epub 2013 Apr 10. PMID: 23576557; PMCID: PMC3674118. 19: Jimeno A, Weiss GJ, Miller WH Jr, Gettinger S, Eigl BJ, Chang AL, Dunbar J, Devens S, Faia K, Skliris G, Kutok J, Lewis KD, Tibes R, Sharfman WH, Ross RW, Rudin CM. Phase I study of the Hedgehog pathway inhibitor IPI-926 in adult patients with solid tumors. Clin Cancer Res. 2013 May 15;19(10):2766-74. doi: 10.1158/1078-0432.CCR-12-3654. Epub 2013 Apr 10. PMID: 23575478; PMCID: PMC3694426. 20: Smith S, Hoyt J, Whitebread N, Manna J, Peluso M, Faia K, Campbell V, Tremblay M, Nair S, Grogan M, Castro A, Campbell M, Ferguson J, Arsenault B, Nevejans J, Carter B, Lee J, Dunbar J, McGovern K, Read M, Adams J, Constan A, Loewen G, Sydor J, Palombella V, Soglia J. The pre-clinical absorption, distribution, metabolism and excretion properties of IPI-926, an orally bioavailable antagonist of the hedgehog signal transduction pathway. Xenobiotica. 2013 Oct;43(10):875-85. doi: 10.3109/00498254.2013.780671. Epub 2013 Mar 25. PMID: 23527529.