APY0201
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MedKoo CAT#: 522383

CAS#: 1232221-74-7

Description: APY0201 is a potent and selective IL-12/23 inhibitor. APY0201 demonstrates ameliorated inflammation in an experimental model of colitis. Interleukin-12 (IL-12) and IL-23 are proinflammatory cytokines and therapeutic targets for inflammatory and autoimmune diseases, including inflammatory bowel diseases, psoriasis, rheumatoid arthritis, and multiple sclerosis.

Chemical Structure

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APY0201
CAS# 1232221-74-7
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 522383
Name: APY0201
CAS#: 1232221-74-7
Chemical Formula: C23H23N7O
Exact Mass: 413.20
Molecular Weight: 413.480
Elemental Analysis: C, 66.81; H, 5.61; N, 23.71; O, 3.87

Price and Availability

Size Price Availability Quantity
5mg USD 90 Ready to ship
10mg USD 160 Ready to ship
25mg USD 350 Ready to ship
50mg USD 550 Ready to ship
100mg USD 950 Ready to ship
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Synonym: APY0201; APY-0201; APY 0201.

IUPAC/Chemical Name: (E)-4-(5-(2-(3-methylbenzylidene)hydrazinyl)-2-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidin-7-yl)morpholine

InChi Key: RFZQYGBLRIKROZ-PCLIKHOPSA-N

InChi Code: InChI=1S/C23H23N7O/c1-17-3-2-4-18(13-17)16-25-27-21-15-23(29-9-11-31-12-10-29)30-22(26-21)14-20(28-30)19-5-7-24-8-6-19/h2-8,13-16H,9-12H2,1H3,(H,26,27)/b25-16+

SMILES Code: CC1=CC(/C=N/NC2=NC3=CC(C4=CC=NC=C4)=NN3C(N5CCOCC5)=C2)=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:

Biological target: APY0201 is a PIKfyve inhibitor, which inhibits the conversion of PtdIns3P to PtdIns(3,5)P2 in the presence of [33P]ATP with an IC50 of 5.2 nM. APY0201 also inhibits IL-12/IL-23 production.
In vitro activity: Following treatment with APY0201 for 6 h, activation of TFEB, found in its dephosphorylated state, was observed independently of the HMCL sensitivity profile to the compound. Nuclear translocation of TFEB following PIKfyve exposure was subsequently confirmed in a subcellular localization immunoblotting assay (Figure 2C, D). Dephosphorylated TFEB translocates from the cytoplasm to the nucleus to regulate the expression of target genes associated with autophagy. Therefore, these findings further supported an APY0201-induced autophagy disturbance through PIKfyve inhibition in MM. Reference: Haematologica. 2020 Jun; 105(6): 1641–1649. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271606/
In vivo activity: To determine the impact of PIFKfyve inhibition on inflammatory responses in vivo, this study evaluated APY0201 in a mouse model of inflammatory bowel disease (IBD) induced by the adoptive transfer of IL-10 knockout (KO) CD4+ T cells. An increase in the colon weight ratio was observed in the vehicle control group for colitis compared with that in the normal control group. Daily administration of APY0201 significantly reduced increases in colon weight in a dose-dependent manner (Fig. 7a; 19.7%, 25.4%, and 73.3% reduction at 3, 10, and 30 mg/kg, respectively), and the effect of APY0201 at 30 mg/kg was equivalent to that of prednisolone (PSL) at 15 mg/kg B.I.D. (81.0% reduction, Fig. 7b). Examination of the stool consistency showed that the vehicle control group exhibited severe diarrhea on the day of the sacrifice, while APY0201 significantly prevented development of diarrhea in a dose-dependent manner (Fig. 7c and d). Twice a day administration of PSL ameliorated inflammation in this mouse model of colitis. However, treatment with PSL led to a significant decrease in body weight after chronic administration relative to that of the vehicle or normal control groups, although the drug relieved diarrhea and reduced colon weight (please see the Supplementary information). Conversely, administration of APY0201 caused no difference in body weight relative to that of the normal control group. These results clearly demonstrated that APY0201 was orally available and significantly efficacious in a mouse model of colitis induced by adoptive transfer of IL-10 KO CD4+ T cells without showing any sign of adverse effects. Reference: Bioorg Med Chem. 2014 Jun 1;22(11):3021-9. https://pubmed.ncbi.nlm.nih.gov/24767819/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 20.0 48.37
DMSO:PBS (pH 7.2) (1:2) 0.3 0.80
DMF 3.0 7.26

Preparing Stock Solutions

The following data is based on the product molecular weight 413.48 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. de Campos CB, Zhu YX, Sepetov N, Romanov S, Bruins LA, Shi CX, Stein CK, Petit JL, Polito AN, Sharik ME, Meermeier EW, Ahmann GJ, Armenta IDL, Kruse J, Bergsagel PL, Chesi M, Meurice N, Braggio E, Stewart AK. Identification of PIKfyve kinase as a target in multiple myeloma. Haematologica. 2020 Jun;105(6):1641-1649. doi: 10.3324/haematol.2019.222729. Epub 2019 Oct 3. PMID: 31582538; PMCID: PMC7271606. 2. Hayakawa N, Noguchi M, Takeshita S, Eviryanti A, Seki Y, Nishio H, Yokoyama R, Noguchi M, Shuto M, Shima Y, Kuribayashi K, Kageyama S, Eda H, Suzuki M, Hatta T, Iemura S, Natsume T, Tanabe I, Nakagawa R, Shiozaki M, Sakurai K, Shoji M, Andou A, Yamamoto T. Structure-activity relationship study, target identification, and pharmacological characterization of a small molecular IL-12/23 inhibitor, APY0201. Bioorg Med Chem. 2014 Jun 1;22(11):3021-9. doi: 10.1016/j.bmc.2014.03.036. Epub 2014 Apr 13. PMID: 24767819.
In vitro protocol: 1. de Campos CB, Zhu YX, Sepetov N, Romanov S, Bruins LA, Shi CX, Stein CK, Petit JL, Polito AN, Sharik ME, Meermeier EW, Ahmann GJ, Armenta IDL, Kruse J, Bergsagel PL, Chesi M, Meurice N, Braggio E, Stewart AK. Identification of PIKfyve kinase as a target in multiple myeloma. Haematologica. 2020 Jun;105(6):1641-1649. doi: 10.3324/haematol.2019.222729. Epub 2019 Oct 3. PMID: 31582538; PMCID: PMC7271606. 2. Hayakawa N, Noguchi M, Takeshita S, Eviryanti A, Seki Y, Nishio H, Yokoyama R, Noguchi M, Shuto M, Shima Y, Kuribayashi K, Kageyama S, Eda H, Suzuki M, Hatta T, Iemura S, Natsume T, Tanabe I, Nakagawa R, Shiozaki M, Sakurai K, Shoji M, Andou A, Yamamoto T. Structure-activity relationship study, target identification, and pharmacological characterization of a small molecular IL-12/23 inhibitor, APY0201. Bioorg Med Chem. 2014 Jun 1;22(11):3021-9. doi: 10.1016/j.bmc.2014.03.036. Epub 2014 Apr 13. PMID: 24767819.
In vivo protocol: 1. Hayakawa N, Noguchi M, Takeshita S, Eviryanti A, Seki Y, Nishio H, Yokoyama R, Noguchi M, Shuto M, Shima Y, Kuribayashi K, Kageyama S, Eda H, Suzuki M, Hatta T, Iemura S, Natsume T, Tanabe I, Nakagawa R, Shiozaki M, Sakurai K, Shoji M, Andou A, Yamamoto T. Structure-activity relationship study, target identification, and pharmacological characterization of a small molecular IL-12/23 inhibitor, APY0201. Bioorg Med Chem. 2014 Jun 1;22(11):3021-9. doi: 10.1016/j.bmc.2014.03.036. Epub 2014 Apr 13. PMID: 24767819.

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1: Hayakawa N, Noguchi M, Takeshita S, Eviryanti A, Seki Y, Nishio H, Yokoyama R,
Noguchi M, Shuto M, Shima Y, Kuribayashi K, Kageyama S, Eda H, Suzuki M, Hatta T,
Iemura S, Natsume T, Tanabe I, Nakagawa R, Shiozaki M, Sakurai K, Shoji M, Andou
A, Yamamoto T. Structure-activity relationship study, target identification, and
pharmacological characterization of a small molecular IL-12/23 inhibitor,
APY0201. Bioorg Med Chem. 2014 Jun 1;22(11):3021-9. doi:
10.1016/j.bmc.2014.03.036. Epub 2014 Apr 13. PubMed PMID: 24767819.