Apilimod mesylate
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MedKoo CAT#: 407105

CAS#: 870087-36-8 (mesylate)

Description: Apilimod, also known as STA-5326, is a IL-12/IL-23 inhibitor. Apilimod inhibits IL-12 and IL-23 production - cytokines that are involved in autoimmune diseases - through the prevention of nuclear translocation of c-Rel. Synta Pharmaceuticals Corp is developing apilimod for the potential treatment of Crohn's disease (CD) and other autoimmune diseases. Preclinical studies demonstrated the successful inhibition of IL-12 and IL-23 production by the drug.

Chemical Structure

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Apilimod mesylate
CAS# 870087-36-8 (mesylate)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 407105
Name: Apilimod mesylate
CAS#: 870087-36-8 (mesylate)
Chemical Formula: C25H34N6O8S2
Exact Mass: 0.00
Molecular Weight: 610.700
Elemental Analysis: C, 49.17; H, 5.61; N, 13.76; O, 20.96; S, 10.50

Price and Availability

Size Price Availability Quantity
10mg USD 80 Ready to ship
25mg USD 150 Ready to ship
50mg USD 225 Ready to ship
100mg USD 385 Ready to ship
200mg USD 685 Ready to ship
500mg USD 1450 Ready to ship
1g USD 2650 Ready to ship
2g USD 4850 Ready to ship
5g USD 8950 2 Weeks
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Related CAS #: 870087-36-8 (mesylate)   541550-19-0 (free base)   1383916-59-3 (free base)   870087-37-9 (HCl)   870151-86-3 (tosylate)   870087-41-5 (besylate)    

Synonym: STA-5326; STA5326; STA 5326; LAM-002; LAM 002; LAM002; Apilimod; Apilimod mesylate.

IUPAC/Chemical Name: (E)-4-(6-(2-(3-methylbenzylidene)hydrazinyl)-2-(2-(pyridin-2-yl)ethoxy)pyrimidin-4-yl)morpholine dimethanesulfonate

InChi Key: GAJWNIKZLYZYSY-OKUPSQOASA-N

InChi Code: InChI=1S/C23H26N6O2.2CH4O3S/c1-18-5-4-6-19(15-18)17-25-28-21-16-22(29-10-13-30-14-11-29)27-23(26-21)31-12-8-20-7-2-3-9-24-20;2*1-5(2,3)4/h2-7,9,15-17H,8,10-14H2,1H3,(H,26,27,28);2*1H3,(H,2,3,4)/b25-17+;;

SMILES Code: CC1=CC(/C=N/NC2=CC(N3CCOCC3)=NC(OCCC4=NC=CC=C4)=N2)=CC=C1.CS(=O)(O)=O.CS(=O)(O)=O

Appearance: White to off-white 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, not in water

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: Related CAS# 870087-36-8 (mesylate); 541550-19-0 (free base)

Biological target: Apilimod mesylate is an IL-12/IL-23 inhibitor which inhibits IL-12 with IC50s of 1 nM and 2 nM, in IFN-γ/SAC-stimulated human PBMCs and SAC-treated monkey PBMCs, respectively.
In vitro activity: To determine whether apilimod induced cytotoxicity in cancer cells, B-NHL was costained with Annexin V, a marker for early apoptosis, and 7-AAD, a membrane-impermeant marker of nonviable cells. A marked loss of membrane integrity and increased Annexin V staining was observed in apilimod-treated B-NHL, confirming induction of cell death (Figure 3A; supplemental Figure 6A). No marked increases in DEVD-UltraGlo Luciferase cleavage (surrogate for caspase 3/7 activity) were observed in apilimod-treated B-NHL cells at physiologically relevant concentrations (Figure 3B; supplemental Figure 6B), nor were a significant rescue of cell viability with caspase, cathepsin, or necroptosis inhibitors observed across the cell lines tested (Figures 3C-3E; supplemental Figure 6C-E). Interestingly, apilimod appears to disrupt the completion of autophagy as indicated by an increase in the levels of p62 and LC3-II (Figure 3F; supplemental Figure 6F). These data suggest that apilimod blocks autophagy and its effects are distinct from apoptosis, lysosomal membrane permeabilization, and necroptosis. Reference: Blood. 2017 Mar 30;129(13):1768-1778. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766845/
In vivo activity: The effects of apilimod were tested in in vivo models of lymphoma. With oral dosing of 60 mg/kg apilimod dimesylate (∼41 mg/kg apilimod free base; twice a day), 48% tumor growth inhibition was observed in the SU-DHL-6 model. Further evaluation of apilimod in an immunocompetent A20 syngeneic lymphoma model provided the opportunity to investigate apilimod in combination with the immuno-oncology therapeutic, anti-programmed death ligand 1 (PD-L1). Apilimod showed significant synergism in the A20 model, manifesting as 86% tumor growth inhibition for the combination with anti-PD-L1, compared with 51% and 53% in the apilimod and anti-PD-L1 single arms, respectively (Figure 2C). Reference: Blood. 2017 Mar 30;129(13):1768-1778. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766845/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
Water 87.0 142.49
DMSO 31.0 50.78
Ethanol 2.5 4.09

Preparing Stock Solutions

The following data is based on the product molecular weight 610.70 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. Gayle S, Landrette S, Beeharry N, Conrad C, Hernandez M, Beckett P, Ferguson SM, Mandelkern T, Zheng M, Xu T, Rothberg J, Lichenstein H. Identification of apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B-cell non-Hodgkin lymphoma. Blood. 2017 Mar 30;129(13):1768-1778. doi: 10.1182/blood-2016-09-736892. Epub 2017 Jan 19. PMID: 28104689; PMCID: PMC5766845. 2. Sbrissa D, Naisan G, Ikonomov OC, Shisheva A. Apilimod, a candidate anticancer therapeutic, arrests not only PtdIns(3,5)P2 but also PtdIns5P synthesis by PIKfyve and induces bafilomycin A1-reversible aberrant endomembrane dilation. PLoS One. 2018 Sep 21;13(9):e0204532. doi: 10.1371/journal.pone.0204532. PMID: 30240452; PMCID: PMC6150535.
In vitro protocol: 1. Gayle S, Landrette S, Beeharry N, Conrad C, Hernandez M, Beckett P, Ferguson SM, Mandelkern T, Zheng M, Xu T, Rothberg J, Lichenstein H. Identification of apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B-cell non-Hodgkin lymphoma. Blood. 2017 Mar 30;129(13):1768-1778. doi: 10.1182/blood-2016-09-736892. Epub 2017 Jan 19. PMID: 28104689; PMCID: PMC5766845. 2. Sbrissa D, Naisan G, Ikonomov OC, Shisheva A. Apilimod, a candidate anticancer therapeutic, arrests not only PtdIns(3,5)P2 but also PtdIns5P synthesis by PIKfyve and induces bafilomycin A1-reversible aberrant endomembrane dilation. PLoS One. 2018 Sep 21;13(9):e0204532. doi: 10.1371/journal.pone.0204532. PMID: 30240452; PMCID: PMC6150535.
In vivo protocol: 1. Gayle S, Landrette S, Beeharry N, Conrad C, Hernandez M, Beckett P, Ferguson SM, Mandelkern T, Zheng M, Xu T, Rothberg J, Lichenstein H. Identification of apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B-cell non-Hodgkin lymphoma. Blood. 2017 Mar 30;129(13):1768-1778. doi: 10.1182/blood-2016-09-736892. Epub 2017 Jan 19. PMID: 28104689; PMCID: PMC5766845.

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1: Cinato M, Guitou L, Saidi A, Timotin A, Sperazza E, Duparc T, Zolov SN, Giridharan SSP, Weisman LS, Martinez LO, Roncalli J, Kunduzova O, Tronchere H, Boal F. Apilimod alters TGFβ signaling pathway and prevents cardiac fibrotic remodeling. Theranostics. 2021 Apr 19;11(13):6491-6506. doi: 10.7150/thno.55821. PMID: 33995670; PMCID: PMC8120213.


2: Baranov MV, Bianchi F, van den Bogaart G. The PIKfyve Inhibitor Apilimod: A Double-Edged Sword against COVID-19. Cells. 2020 Dec 27;10(1):30. doi: 10.3390/cells10010030. PMID: 33375410; PMCID: PMC7824419.


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4: Bowles KR, Silva MC, Whitney K, Bertucci T, Berlind JE, Lai JD, Garza JC, Boles NC, Mahali S, Strang KH, Marsh JA, Chen C, Pugh DA, Liu Y, Gordon RE, Goderie SK, Chowdhury R, Lotz S, Lane K, Crary JF, Haggarty SJ, Karch CM, Ichida JK, Goate AM, Temple S. ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids. Cell. 2021 Aug 19;184(17):4547-4563.e17. doi: 10.1016/j.cell.2021.07.003. Epub 2021 Jul 26. PMID: 34314701; PMCID: PMC8635409.


5: Lu JT, Xiao MK, Feng YY, Wang XY, Qiu LL, Chai YR, Wang TY, Jia YL. Apilimod enhances specific productivity in recombinant CHO cells through cell cycle arrest and mediation of autophagy. Biotechnol J. 2023 Feb;18(2):e2200147. doi: 10.1002/biot.202200147. Epub 2022 Dec 14. PMID: 36478399.


6: Sbrissa D, Naisan G, Ikonomov OC, Shisheva A. Apilimod, a candidate anticancer therapeutic, arrests not only PtdIns(3,5)P2 but also PtdIns5P synthesis by PIKfyve and induces bafilomycin A1-reversible aberrant endomembrane dilation. PLoS One. 2018 Sep 21;13(9):e0204532. doi: 10.1371/journal.pone.0204532. PMID: 30240452; PMCID: PMC6150535.


7: Gayle S, Landrette S, Beeharry N, Conrad C, Hernandez M, Beckett P, Ferguson SM, Mandelkern T, Zheng M, Xu T, Rothberg J, Lichenstein H. Identification of apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B-cell non-Hodgkin lymphoma. Blood. 2017 Mar 30;129(13):1768-1778. doi: 10.1182/blood-2016-09-736892. Epub 2017 Jan 19. PMID: 28104689; PMCID: PMC5766845.


8: Nelson EA, Dyall J, Hoenen T, Barnes AB, Zhou H, Liang JY, Michelotti J, Dewey WH, DeWald LE, Bennett RS, Morris PJ, Guha R, Klumpp-Thomas C, McKnight C, Chen YC, Xu X, Wang A, Hughes E, Martin S, Thomas C, Jahrling PB, Hensley LE, Olinger GG Jr, White JM. The phosphatidylinositol-3-phosphate 5-kinase inhibitor apilimod blocks filoviral entry and infection. PLoS Negl Trop Dis. 2017 Apr 12;11(4):e0005540. doi: 10.1371/journal.pntd.0005540. PMID: 28403145; PMCID: PMC5402990.


9: Wada Y, Cardinale I, Khatcherian A, Chu J, Kantor AB, Gottlieb AB, Tatsuta N, Jacobson E, Barsoum J, Krueger JG. Apilimod inhibits the production of IL-12 and IL-23 and reduces dendritic cell infiltration in psoriasis. PLoS One. 2012;7(4):e35069. doi: 10.1371/journal.pone.0035069. Epub 2012 Apr 6. PMID: 22493730; PMCID: PMC3320873.


10: Billich A. Drug evaluation: apilimod, an oral IL-12/IL-23 inhibitor for the treatment of autoimmune diseases and common variable immunodeficiency. IDrugs. 2007 Jan;10(1):53-9. PMID: 17187316.


11: Mamontov E, Cheng Y, Daemen LL, Kolesnikov AI, Ramirez-Cuesta AJ, Ryder MR, Stone MB. Low rotational barriers for the most dynamically active methyl groups in the proposed antiviral drugs for treatment of SARS-CoV-2, apilimod and tetrandrine. Chem Phys Lett. 2021 Aug 16;777:138727. doi: 10.1016/j.cplett.2021.138727. Epub 2021 May 8. PMID: 33994552; PMCID: PMC8105138.


12: Krausz S, Boumans MJ, Gerlag DM, Lufkin J, van Kuijk AW, Bakker A, de Boer M, Lodde BM, Reedquist KA, Jacobson EW, O'Meara M, Tak PP. Brief report: a phase IIa, randomized, double-blind, placebo-controlled trial of apilimod mesylate, an interleukin-12/interleukin-23 inhibitor, in patients with rheumatoid arthritis. Arthritis Rheum. 2012 Jun;64(6):1750-5. doi: 10.1002/art.34339. Epub 2011 Dec 14. PMID: 22170479.


13: Gayle S, Landrette S, Beeharry N, Conrad C, Hernandez M, Beckett P, Ferguson SM, Xu T, Rothberg J, Lichenstein H. B-cell non-Hodgkin lymphoma: Selective vulnerability to PIKFYVE inhibition. Autophagy. 2017 Jun 3;13(6):1082-1083. doi: 10.1080/15548627.2017.1304871. Epub 2017 Mar 28. PMID: 28350209; PMCID: PMC5486370.


14: Sands BE, Jacobson EW, Sylwestrowicz T, Younes Z, Dryden G, Fedorak R, Greenbloom S. Randomized, double-blind, placebo-controlled trial of the oral interleukin-12/23 inhibitor apilimod mesylate for treatment of active Crohn's disease. Inflamm Bowel Dis. 2010 Jul;16(7):1209-18. doi: 10.1002/ibd.21159. PMID: 19918967.


15: Cai X, Xu Y, Cheung AK, Tomlinson RC, Alcázar-Román A, Murphy L, Billich A, Zhang B, Feng Y, Klumpp M, Rondeau JM, Fazal AN, Wilson CJ, Myer V, Joberty G, Bouwmeester T, Labow MA, Finan PM, Porter JA, Ploegh HL, Baird D, De Camilli P, Tallarico JA, Huang Q. PIKfyve, a class III PI kinase, is the target of the small molecular IL-12/IL-23 inhibitor apilimod and a player in Toll-like receptor signaling. Chem Biol. 2013 Jul 25;20(7):912-21. doi: 10.1016/j.chembiol.2013.05.010. PMID: 23890009; PMCID: PMC4878021.


16: Xu J, Li J, Hu Y, Dai K, Gan Y, Zhao J, Huang M, Zhang X. IL-23, but not IL-12, plays a critical role in inflammation-mediated bone disorders. Theranostics. 2020 Mar 4;10(9):3925-3938. doi: 10.7150/thno.41378. PMID: 32226529; PMCID: PMC7086346.


17: Ikonomov OC, Sbrissa D, Shisheva A. Small molecule PIKfyve inhibitors as cancer therapeutics: Translational promises and limitations. Toxicol Appl Pharmacol. 2019 Nov 15;383:114771. doi: 10.1016/j.taap.2019.114771. Epub 2019 Oct 16. PMID: 31628917.


18: Sultana F, Morse LR, Picotto G, Liu W, Jha PK, Odgren PR, Battaglino RA. Snx10 and PIKfyve are required for lysosome formation in osteoclasts. J Cell Biochem. 2020 Apr;121(4):2927-2937. doi: 10.1002/jcb.29534. Epub 2019 Nov 6. PMID: 31692073.


19: Kang YL, Chou YY, Rothlauf PW, Liu Z, Soh TK, Cureton D, Case JB, Chen RE, Diamond MS, Whelan SPJ, Kirchhausen T. Inhibition of PIKfyve kinase prevents infection by Zaire ebolavirus and SARS-CoV-2. bioRxiv [Preprint]. 2020 Jun 15:2020.04.21.053058. doi: 10.1101/2020.04.21.053058. Update in: Proc Natl Acad Sci U S A. 2020 Aug 25;117(34):20803-20813. PMID: 32511398; PMCID: PMC7263545.


20: Kang YL, Chou YY, Rothlauf PW, Liu Z, Soh TK, Cureton D, Case JB, Chen RE, Diamond MS, Whelan SPJ, Kirchhausen T. Inhibition of PIKfyve kinase prevents infection by Zaire ebolavirus and SARS-CoV-2. Proc Natl Acad Sci U S A. 2020 Aug 25;117(34):20803-20813. doi: 10.1073/pnas.2007837117. Epub 2020 Aug 6. PMID: 32764148; PMCID: PMC7456157.