Apilimod free base
featured

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

MedKoo CAT#: 326647

CAS#: 541550-19-0 (free base)

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

img
Apilimod free base
CAS# 541550-19-0 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 326647
Name: Apilimod free base
CAS#: 541550-19-0 (free base)
Chemical Formula: C23H26N6O2
Exact Mass: 418.21
Molecular Weight: 418.501
Elemental Analysis: C, 66.01; H, 6.26; N, 20.08; O, 7.65

Price and Availability

Size Price Availability Quantity
10mg USD 80 Ready to ship
25mg USD 150 Ready to ship
50mg USD 250 Ready to ship
100mg USD 450 Ready to ship
200mg USD 750 Ready to ship
500mg USD 1550 Ready to ship
1g USD 2450 Ready to ship
2g USD 4350 Ready to ship
5g USD 7450 2 Weeks
Bulk inquiry

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 free base.

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

InChi Key: HSKAZIJJKRAJAV-KOEQRZSOSA-N

InChi Code: InChI=1S/C23H26N6O2/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/h2-7,9,15-17H,8,10-14H2,1H3,(H,26,27,28)/b25-17+

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

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, 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: 541550-19-0 (Apilimod free base) 870087-36-8 (Apilimod mesylate)

Biological target: Apilimod (STA 5326) is a potent IL-12/IL-23 inhibitor, and strongly 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: Apilimod was profiled for its antiproliferative activity against 146 cell lines representing 11 tumor types. Although cells from many cancer lineages responded to apilimod, it was observed that B-NHL lines were the most broadly sensitive (supplemental Figure 2). We noted antiproliferative activity in all B-NHL subtypes with ∼73% of lines having an IC50 < 200 nM (Figure 1A) and defined these as sensitive. Notably, significant antiproliferative activity was observed on cell lines derived from difficult to treat double- and triple-hit B-NHL. Although apilimod was initially identified through screening of an mTORC1-hyperactivated cell line, potent antiproliferative activity in B-NHL lines irrespective of mTORC1 activation were observed (supplemental Table 1; supplemental Figure 3). Furthermore, apilimod did not affect mTORC1 signaling (supplemental Figure 3B). Overall, apilimod had selective antiproliferative activity for B-NHL compared with normal cells with IC50 of 142 nM and 12 782 nM, respectively (Figure 1B-C; see supplemental Tables 1 and 2 for cell line–specific data in lymphoma and normal cells). Reference: Blood. 2017 Mar 30;129(13):1768-1778. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/28104689/
In vivo activity: To address the effects of Apilimod in cardiac fibrotic remodeling, a mouse model of transverse aortic constriction (TAC) was used. Cardiac pressure overload induced by four weeks TAC triggered a massive myocardial deposition of ECM proteins as shown by Sirius red staining, typical for end-stage fibrotic tissue remodeling (Figure 1A-B). Strikingly, Apilimod abrogated myocardial collagen fibre accumulation in TAC-mice (Figure 1A-B). Consistently, daily Apilimod treatment attenuated TAC-induced overexpression of cardiac pro-fibrotic genes including collagen 1 (Col1, Figure 1C), collagen 3 (Col3, Figure 1D), fibronectin 1 (Figure 1E) and connective tissue growth factor (Ctgf, Figure 1F). Moreover, upon Apilimod treatment, TAC-induced expression of periostin, a well-known marker of activated cardiac fibroblasts 29, was strongly inhibited (Figure 1G), suggesting that Apilimod prevents fibroblast activation in vivo. Consistently, TAC-stressed mice treated with Apilimod showed reduced level of α-SMA as demonstrated by immunofluorescent staining (Figure S1A). Moreover, we found that Apilimod decreased the recruitment of CD-68-positive macrophages (Figure S1B) and the production of the myocardial pro-inflammatory cytokines Il-6 (Figure S1C), Tnf-α (Figure S1D) and Ccl2 (Figure S1E). In addition, we found that Apilimod reduced cardiac hypertrophy induced by TAC, as shown morphologically (Figure 2A-B) and by the expression of the hypertrophic markers Anp (Figure 2C), Bnp (Figure 2D), α-skeletal actin (Figure 2E) and β-Mhc (Figure 2F). Consistently, echocardiography analysis showed that Apilimod reduced end-diastolic ventricular wall thickness, intraventricular septum thickness and left ventricular mass (Table 1) in TAC-stressed mice hearts. It has to be noted that Apilimod-treatment does not completely abrogate the hypertrophic response following TAC. Importantly, the myocardial anti-fibrotic effect of Apilimod culminated in the preservation of cardiac function in TAC-mice, as shown by improved EF and shortening fraction (Table 1 and Figure S1F, EF and SF respectively). These results suggest that Apilimod is a potent inhibitor of fibroblast activation and myocardial fibrosis development in vivo, leading to preserved cardiac performance following TAC surgery. Reference: Theranostics. 2021 Apr 19;11(13):6491-6506. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/33995670/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 46.0 109.92

Preparing Stock Solutions

The following data is based on the product molecular weight 418.50 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:
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.
In vivo protocol: 1. Wada Y, Lu R, Zhou D, Chu J, Przewloka T, Zhang S, Li L, Wu Y, Qin J, Balasubramanyam V, Barsoum J, Ono M. Selective abrogation of Th1 response by STA-5326, a potent IL-12/IL-23 inhibitor. Blood. 2007 Feb 1;109(3):1156-64. doi: 10.1182/blood-2006-04-019398. Epub 2006 Oct 19. PMID: 17053051. 2. 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.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

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.


3: Riva L, Yuan S, Yin X, Martin-Sancho L, Matsunaga N, Pache L, Burgstaller- Muehlbacher S, De Jesus PD, Teriete P, Hull MV, Chang MW, Chan JF, Cao J, Poon VK, Herbert KM, Cheng K, Nguyen TH, Rubanov A, Pu Y, Nguyen C, Choi A, Rathnasinghe R, Schotsaert M, Miorin L, Dejosez M, Zwaka TP, Sit KY, Martinez- Sobrido L, Liu WC, White KM, Chapman ME, Lendy EK, Glynne RJ, Albrecht R, Ruppin E, Mesecar AD, Johnson JR, Benner C, Sun R, Schultz PG, Su AI, García-Sastre A, Chatterjee AK, Yuen KY, Chanda SK. Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing. Nature. 2020 Oct;586(7827):113-119. doi: 10.1038/s41586-020-2577-1. Epub 2020 Jul 24. PMID: 32707573; PMCID: PMC7603405.


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.