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Fig. 1 · Structure
Cat. No.
A11064
CAS No.
371942-69-7
Formula
C25H21N7O3
Mol. Weight
467.5

Documents & Downloads

YM201636

Cat. No. A11064 CAS 371942-69-7

PI3K Inhibitor

YM201636 is a cell-permeable and selective inhibitor of PIKfyve (IC50 = 33 nM).

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Publications for YM201636

2 publications citing this product

  1. Krishna Chintaluri, .et al. , PLoS One, 2018, 13(6): e0198454 PMID: 29870544
  2. Dayam RM, .et al. , J Immunol, 2017, Sep 15;199(6):2096-2105 PMID: 28779020
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Biological Activity

Bioactivity / Mechanism

YM201636 inhibited PIKfyve in a biochemical assay with an IC50 of 0.033 μM at 50 μM ATP. In the same panel, the reported IC50 values were 3.3 μM for p110α and >5 μM for yeast Fab1. This selectivity comparison is specific to the tested enzymes and assay conditions. [1]

Selectivity depends on the experimental system. At 100 nM, YM201636 suppressed insulin-responsive PI3K product formation in PIKfyve-containing immunoprecipitates from adipocytes. This native preparation differs from the biochemical p110α panel; the reason for the differing sensitivities remains unproven. [2]

YM201636 also inhibited human TPC2 currents activated by exogenous PI(3,5)P2 in excised membrane patches (IC50 0.16 μM). This additional activity limits attribution of cellular responses solely to PIKfyve inhibition. [3]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

Target & Activity

Target Activity Value
PIKfyve 33 nM
p110α 3.3 μM

In Vitro Studies

In differentiated 3T3L1 adipocytes, YM201636 inhibited basal and insulin-stimulated glucose uptake. The reported IC50 for the net insulin response above basal was 54 ± 4 nM; this cellular endpoint is distinct from biochemical PIKfyve inhibition. [2]

YM201636 reduced MTT optical density in HepG2 and Huh-7 cells after 24 h across a 0.1–5 μM concentration series. This assay supports a reduced metabolic viability signal, without by itself distinguishing growth arrest from cell death. [4]

Biochemical PIKfyve inhibition and comparator kinase panel

Biochemical assay · PIKfyve, yeast Fab1 and p110α lipid kinase assays at 50 μM ATP [1]

PIKfyve was more sensitive than the tested Fab1 and p110α enzymes. These assay-specific values do not establish universal cellular selectivity.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
PIKfyve lipid kinase activityIC50 0.033 μM (0.027–0.041 μM; 95% confidence limits); data points in triplicate[1]
Yeast Fab1 activityIC50 >5 μM; data points in triplicate[1]
p110α activityIC50 3.3 μM (2.8–3.9 μM; 95% confidence limits); data points in triplicate[1]

Literature-Reported Treatment Conditions

Method
In vitro lipid kinase activity concentration-response assays at 50 μM ATP; GraphPad Prism IC50 fitting.
Reported limits
Full concentration series and assay duration are not specified in the acquired main text; supplementary PDF was not retrieved.
Methods and source locations

Compound reported in the paper: YM201636; Compound label in the paper: YM201636

Evidence applies to the named research compound in the reported model; equivalence to an Adooq lot was not tested.

Table 1 with footnote; Results first paragraph; Methods: In vitro lipid kinase assays; Fig. 1A

PIKfyve lipid kinase activity: Lipid kinase activity assay at 50 μM ATP. — Table 1, YM201636 row and footnote

Yeast Fab1 activity: Same panel and ATP condition. — Table 1, YM201636 row and footnote

p110α activity: Same panel and ATP condition. — Table 1, YM201636 row and footnote

Suppression of glucose uptake in differentiated adipocytes

Cell-based study · Differentiated mouse 3T3L1 adipocytes; basal and insulin-stimulated 2-deoxyglucose uptake [2]

YM201636 suppressed basal and insulin-stimulated uptake. The reported IC50 concerns the net insulin response above basal; it is not an enzyme IC50.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Net insulin-stimulated uptake above basalIC50 54 ± 4 nM; mean ± SEM; Fig. 1 reports three independent experiments in triplicate[2]
Net insulin-stimulated uptakeQualitative response Nearly completely inhibited at 160 nM[2]

Literature-Reported Treatment Conditions

Treatment concentration
0–4 μM; Fig. 1B labels 0, 10, 30, 60, 160, 800 and 4000 nM
Exposure duration
30 min pretreatment, followed by 100 nM insulin or no insulin for 30 min; tracer uptake 5 min
Method
Radiolabeled 2-deoxyglucose uptake, corrected using cytochalasin B and normalized to protein.
Co-treatment
Insulin is a stimulation condition (100 nM), with matched basal controls.
Reported limits
Vehicle composition for this glucose-uptake experiment is not specified in the acquired text.
Methods and source locations

Compound reported in the paper: YM201636; Compound label in the paper: YM201636

Evidence applies to the named research compound in the reported model; equivalence to an Adooq lot was not tested.

Fig. 1A-B and caption; Results first paragraph; Methods: Cell cultures and cell treatments, 2-Deoxyglucose uptake, Statistical analysis

Net insulin-stimulated uptake above basal: Net response calculated against cells without YM201636. — Results first paragraph; Fig. 1B and caption

Net insulin-stimulated uptake: Reported text, with Fig. 1 viewed; no percentage estimated from the curve. — Results first paragraph; Fig. 1A-B

Inhibition of adipocyte-derived PI3K activity

Biochemical assay · Anti-PIKfyve immunoprecipitates from basal or insulin-stimulated 3T3L1 adipocytes [2]

YM201636 reduced native insulin-responsive class IA PI3K product formation in a PIKfyve-containing immunoprecipitate. This differs from a purified p110α assay and does not identify a particular PI3K isoform as the direct target.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
GroPIns3P after insulin stimulation, relative to basal GroPIns3P in panel aRelative product formation Without YM201636: 546 ± 39% (p < 0.001; n = 3); with YM201636: 111 ± 16% (insignificant insulin-dependent increase); mean ± SEM[2]
Basal GroPIns3P formationDecrease 52 ± 6% decrease (p < 0.001; n = 3; mean ± SEM)[2]

Literature-Reported Treatment Conditions

Treatment concentration
100 nM in the kinase assay
Exposure duration
15 min preincubation, then 15 min kinase assay at 37°C
Method
TLC followed by HPLC to distinguish radiolabeled PtdIns3P and PtdIns5P; 15 μM ATP.
Vehicle
Vehicle control; composition not specified
Co-treatment
Cells stimulated with or without insulin (100 nM, 10 min) before immunoprecipitation.
Reported limits
No purified PI3K isoform assignment; vehicle composition unreported in acquired methods.
Methods and source locations

Compound reported in the paper: YM201636; Compound label in the paper: YM201636

Evidence applies to the named research compound in the reported model; equivalence to an Adooq lot was not tested.

Fig. 4A-B and caption; Results final paragraph; Methods: Lipid kinase assay, TLC and HPLC analyses; Statistical analysis; Discussion final paragraph (native versus recombinant preparations and unresolved attribution)

GroPIns3P after insulin stimulation, relative to basal GroPIns3P in panel a: HPLC peak area integration after TLC product recovery; denominator is basal in panel a. — Fig. 4B caption, panels a-b and d

Basal GroPIns3P formation: Comparison with basal no-inhibitor sample by HPLC. — Fig. 4B caption, panel c versus a

Concentration-dependent MTT response in hepatoma cell lines

Cell-based study · HepG2 and Huh-7 cells [4]

MTT optical density decreased with increasing YM201636 concentration. This metabolic assay alone does not distinguish cytostasis from cell death.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
MTT optical density in HepG2 and Huh-7Concentration-response Concentration-dependent decrease; n=5/group; mean ± standard error. One-way ANOVA followed by Dunnett’s test.[4]

Literature-Reported Treatment Conditions

Treatment concentration
0.1, 0.2, 0.5, 1, 2 and 5 μM
Exposure duration
24 h
Method
MTT assay at 490 nm against vehicle-treated controls.
Reported limits
Cellular treatment vehicle composition not specified in the MTT method; DMSO used later to dissolve MTT crystals is not assigned as the treatment vehicle.
Methods and source locations

Compound reported in the paper: YM201636; Compound label in the paper: YM201636

Evidence applies to the named research compound in the reported model; equivalence to an Adooq lot was not tested.

Fig. 1A-B and caption; Methods: Reagents and antibodies, Cell lines and cell culture, MTT assay, Statistical analysis; Results: Effects of YM201636 on HepG2 and Huh-7 cell viability

MTT optical density in HepG2 and Huh-7: Vehicle-treated controls; experiments repeated at least 3 times in Methods. Figure n=5 is not assumed to mean five independent biological repeats. — Fig. 1A-B and caption; corresponding Results

TPC2 current inhibition in excised membrane patches

Cell-based study · Inside-out patches from HEK293 cells expressing human TPC2 L11A/L12A (TPC2PM) [3]

YM201636 inhibited TPC2 Na+ currents elicited by exogenous PI(3,5)P2. This channel-current assay adds a selectivity limitation to interpreting cellular responses solely through PIKfyve.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
PI(3,5)P2-elicited human TPC2PM Na+ currentIC50 0.16 μM; n=6–8 per concentration; averaged data mean ± SEM[3]

Literature-Reported Treatment Conditions

Treatment concentration
Concentration-response series; 0.16 μM is the fitted IC50, not a fixed treatment dose
Method
Cytosolic-side perfusion during inside-out patch recording at room temperature; asymmetric extracellular Na+/intracellular K+ solutions.
Co-treatment
Currents activated by 0.3 μM PI(3,5)P2.
Reported limits
Exposure duration and vehicle composition for Fig. 2a-b not specified in acquired caption/methods; no duration imported from other configurations.
Methods and source locations

Compound reported in the paper: YM201636; Compound label in the paper: YM201636

Evidence applies to the named research compound in the reported model; equivalence to an Adooq lot was not tested.

Fig. 2a-b and caption; Results: YM201636 directly inhibits TPC2 channels; Methods: Cell culture and cDNA transfection, Electrophysiology, Statistics and reproducibility

PI(3,5)P2-elicited human TPC2PM Na+ current: Inside-out patch-clamp, Hill concentration-response fit; PI(3,5)P2 0.3 μM. — Results: YM201636 directly inhibits TPC2 channels; Fig. 2a-b and caption

In Vivo Studies

In a subcutaneous H22 allograft model, oral YM201636 at 2 mg/kg once daily for 7 days reduced terminal tumor weight relative to 5% DMSO controls. Treatment began 1 day after inoculation. Organ weight indices did not differ significantly; this limited short-course observation does not establish broad safety. [4]

Short-course YM201636 in an H22 tumor allograft model

Animal study · Male BALB/c mice, 5 weeks old, 20–25 g, bearing subcutaneous H22 mouse hepatoma allografts [4]

Seven daily oral doses were associated with reduced excised tumor weight versus 5% DMSO controls. Organ weight indices did not differ significantly; this short-course endpoint does not establish comprehensive safety.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Excised tumor weightMean ± standard error YM201636: 0.31±0.05 g; control: 0.67±0.07 g; n=10/group; p<0.001[4]
Heart, liver, spleen, lung and kidney weight indicesBetween-group comparison No significant difference; caption n=10[4]

Conditions shared by the study groups

Route
Oral
Frequency
Once daily
Treatment course
7 consecutive days, starting 1 day after inoculation
Study groups and reported outcomes
Group / doseComparatorObserved resultReference
YM201636
2 mg/kg		5% DMSO-treated groupTumor weight 0.31±0.05 g versus 0.67±0.07 g in controls; n=10/group; p<0.001. No significant organ-index differences.[4]
YM201636
Model: Male BALB/c mice, 5 weeks old, 20–25 g, bearing subcutaneous H22 mouse hepatoma allografts
Reported limits: Complete compound formulation and blinding not specified in the acquired section.
Methods and source locations

Compound reported in the paper: YM201636; Compound label in the paper: YM201636

Evidence applies to the named research compound in the reported model; equivalence to an Adooq lot was not tested.

Fig. 10A-B,E and caption; Methods: Evaluation of antitumor effects in vivo, Statistical analysis; Results: YM201636 inhibits the in situ growth of hepatoma in vivo

Excised tumor weight: Terminal tumor weighing; two-tailed unpaired t-test. — Results animal paragraph; Fig. 10B and caption

Heart, liver, spleen, lung and kidney weight indices: Terminal organ/bodyweight comparison. No exact organ values extracted; Methods describes percentage whereas axis uses mg/g. — Fig. 10E and caption; Methods animal section

YM201636 · Methods: Evaluation of antitumor effects in vivo; Results animal paragraph; Fig. 10A-B,E

Specifications

Manufacturer Adooq Bioscience
Actions Inhibitor
CAS Number 371942-69-7
Applications PI3K Inhibitor
Formula C25H21N7O3
Molecular Weight 467.5
SMILES
C1COCCN1C2=NC(=NC3=C2OC4=C3C=CC=N4)C5=CC(=CC=C5)NC(=O)C6=CN=C(C=C6)N

Storage & Solubility

In Vitro Solubility

Reported Solubility

SolventReported Solubility
DMSO 31 mg/mL (66.3 mM)
Water Insoluble
Ethanol Insoluble

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

  1. [1] Jefferies HB, Cooke FT, Jat P, et al. A selective PIKfyve inhibitor blocks PtdIns(3,5)P(2) production and disrupts endomembrane transport and retroviral budding. EMBO reports (2008). PMID: 18188180 DOI: 10.1038/sj.embor.7401155 Source material
  2. [2] Ikonomov OC, Sbrissa D, Shisheva A. YM201636, an inhibitor of retroviral budding and PIKfyve-catalyzed PtdIns(3,5)P2 synthesis, halts glucose entry by insulin in adipocytes. Biochemical and biophysical research communications (2009). PMID: 19289105 DOI: 10.1016/j.bbrc.2009.03.063 Source material
  3. [3] Du C, Guan X, Yan J. Two-pore channel blockade by phosphoinositide kinase inhibitors YM201636 and PI-103 determined by a histidine residue near pore-entrance. Communications biology (2022). PMID: 35871252 DOI: 10.1038/s42003-022-03701-5 Source material
  4. [4] Hou JZ, Xi ZQ, Niu J, et al. Inhibition of PIKfyve using YM201636 suppresses the growth of liver cancer via the induction of autophagy. Oncology reports (2019). PMID: 30569119 DOI: 10.3892/or.2018.6928 Source material

Publications

2 publications citing this product

  1. Krishna Chintaluri, .et al. , PLoS One, 2018, 13(6): e0198454 PMID: 29870544
  2. Dayam RM, .et al. , J Immunol, 2017, Sep 15;199(6):2096-2105 PMID: 28779020

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