We use analytics and advertising cookies, which you can accept or reject; see our privacy policy.

Current choice:

Fig. 1 · Structure
Cat. No.
A11319
CAS No.
439575-02-7
Formula
C32H41N5O4S2
Mol. Weight
623.8

Documents & Downloads

BMS-509744

Cat. No. A11319 CAS 439575-02-7

Itk Inhibitor

The ITK inhibitor BMS-509744 disrupts several aspects of HIV replication.

In Stock

Publications for BMS-509744

2 publications citing this product

  1. Samson AA, .et al. , Methods Mol Biol, 2017, 1571:221-232 PMID: 28281259
  2. YK Tak, .et al. , Anal. Chem., 2013, 85 (9), pp 4273-4278 PMID: 23573871
Notify me when the price drops

For laboratory research use only. We do not sell to patients.

Free Aliquoting for Your Order

Tell us your preferred amount per vial. We’ll confirm the options.

Biological Activity

Bioactivity / Mechanism

BMS-509744 showed reversible binding to recombinant ITK in a dilution-based dissociation assay. Its reported residence time was 32 ± 17 min, whereas covalent comparator PRN694 remained bound over the assay period. [1]

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

In Vitro Studies

In primary T-PLL cells from five cases, ex vivo BMS-509744 treatment at 0.01–1.5 μM did not appreciably reduce viability after 24 or 48 h. This negative result limits extrapolation of ITK inhibition to direct cytotoxicity in T-PLL. [2]

Reversible binding to recombinant ITK

Biochemical assay · Recombinant His6-labeled ITK; biochemical ligand-dissociation assay [1]

BMS-509744 dissociated rapidly after dilution, in contrast to the persistent binding of covalent comparator PRN694. The caption reports a residence time of 32 ± 17 min; this is not an IC50.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
ITK ligand residence time (τ)Residence time 32 ± 17 min[1]

Literature-Reported Treatment Conditions

Treatment concentration
1.5 μM BMS-509744 with 0.5 μM recombinant ITK
Exposure duration
90 min binding incubation; sampling at 0.25, 1, 3, 6 and 24 h after dilution
Method
50-fold dilution followed by tracer binding measured using time-resolved FRET
Reported limits
Vehicle, replicate count and definition of ± for the fitted residence-time estimate are not specified in the adopted off-rate description.
Methods and source locations

Compound reported in the paper: BMS-509744; Compound label in the paper: BMS-509744

Results concern the material and conditions tested by the authors; no salt conversion or catalog-lot performance claim.

Experimental Procedures: Determination of PRN694 Off-rate with Recombinant ITK; Results: Structure, Potency, and Specificity of PRN694; Figure 1C and caption.

ITK ligand residence time (τ): Time-resolved FRET off-rate assay; Figure 1C and caption — Experimental Procedures: Determination of PRN694 Off-rate with Recombinant ITK; Results: Structure, Potency, and Specificity of PRN694; Figure 1C and caption.

Limited ex vivo effect on primary T-PLL cell viability

Cell-based study · Primary human T-cell prolymphocytic leukemia cells, n = 5 cases; ex vivo treatment [2]

BMS-509744 did not appreciably reduce primary T-PLL cell viability over the tested concentration range at 24 or 48 h. This is an ex vivo observation, not patient treatment.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Viability of primary T-PLL cellsQualitative viability response No appreciable loss of viability reported; n = 5 cases[2]

Literature-Reported Treatment Conditions

Treatment concentration
0.01, 0.05, 0.1, 0.5, 1 and 1.5 μM; zero-dose control
Exposure duration
24 and 48 h
Method
Annexin V/7AAD flow cytometry; viable double-negative cells
Reported limits
Vehicle composition, detailed culture medium and error-bar definition for Figure 1E are not specified in this short letter.
Methods and source locations

Compound reported in the paper: BMS-509744; Compound label in the paper: BMS-509744

Results concern the material and conditions tested by the authors; no salt conversion or catalog-lot performance claim.

Letter body paragraph describing low in-vitro efficacy; Figure 1E and caption.

Viability of primary T-PLL cells: Annexin V/7AAD flow cytometry, Figure 1E; no exact bar heights extracted — Letter body paragraph describing low in-vitro efficacy; Figure 1E and caption.

In Vivo Studies

Topical 3% BMS-509744 reduced ear thickening and histological inflammation in a mouse imiquimod model. In a separate application-site comparison, treatment on the inflamed ear reduced thickening, whereas application on the opposite ear did not significantly improve the affected ear. These findings concern local treatment in this model. [3]

Topical treatment reduces imiquimod-induced skin inflammation

Animal study · 7–8-week-old female BALB/c mice with topical imiquimod-induced left-ear psoriasis-like inflammation [3]

Topical BMS-509744 reduced day-5 ear thickening and histological inflammation relative to IMQ/vehicle controls. Ear thickness used 10 mice/group; histology used 5 mice/group. These endpoints belong to the same treatment design.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Day-5 increase in ear thicknessEar thickening Reduced versus IMQ/vehicle, p < 0.05; n = 10 mice/group; mean ± SD[3]
Epidermal thickness and dermal infiltrating cells on day 5Histological inflammation Both reduced versus IMQ/vehicle, p < 0.01; n = 5 mice/group; mean ± SD[3]

Conditions shared by the study groups

Route
Topical, front and back of left ear
Frequency
Once daily, 1 h before imiquimod
Treatment course
Days 1–4; outcome on day 5
Vehicle
10% DMSO/90% acetone
Study groups and reported outcomes
Group / doseComparatorObserved resultReference
BMS-509744 on affected left ear
3% BMS-509744		IMQ plus vehicle; normal mice; oral prednisolone 5 mg/kg as separate positive comparatorReduced day-5 ear thickening, epidermal thickness and dermal cell infiltration.[3]
BMS-509744 on affected left ear
Model: 7–8-week-old female BALB/c mice with topical imiquimod-induced left-ear psoriasis-like inflammation
Reported limits: Application volume and mass per ear are not specified in the adopted main-text regimen.
Methods and source locations

Compound reported in the paper: BMS-509744; Compound label in the paper: BMS-509744

Results concern the material and conditions tested by the authors; no salt conversion or catalog-lot performance claim.

Materials and Methods: Compound, Animals, IMQ-Induced Psoriasis-Like Skin Inflammation, Histology and Immunohistochemistry, Statistical Analysis; Results and Figures 1A–C and 2A–C with captions.

Day-5 increase in ear thickness: Micrometer; Dunnett’s test; Figure 1C — Materials and Methods: Compound, Animals, IMQ-Induced Psoriasis-Like Skin Inflammation, Histology and Immunohistochemistry, Statistical Analysis; Results and Figures 1A–C and 2A–C with captions.

Epidermal thickness and dermal infiltrating cells on day 5: H&E sections with image analysis; Dunnett’s test; Figures 2B–C — Materials and Methods: Compound, Animals, IMQ-Induced Psoriasis-Like Skin Inflammation, Histology and Immunohistochemistry, Statistical Analysis; Results and Figures 1A–C and 2A–C with captions.

BMS-509744 on affected left ear · Materials and Methods: Compound, Animals, IMQ-Induced Psoriasis-Like Skin Inflammation, Histology and Immunohistochemistry, Statistical Analysis; Results and Figures 1A–C and 2A–C with captions.

Application-site control limits systemic interpretation

Animal study · 7–8-week-old female BALB/c mice with topical imiquimod-induced left-ear psoriasis-like inflammation [3]

In a separate application-site comparison, BMS-509744 applied to the inflamed left ear reduced its thickening; applying it to the untreated right ear did not significantly reduce left-ear thickening. The result supports a local effect under this regimen, without measuring systemic exposure.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Day-5 affected left-ear thickeningApplication-site dependence Left-ear treatment: p < 0.05 versus vehicle; right-ear treatment: not significant; n = 10 mice/group; mean ± SD[3]

Conditions shared by the study groups

Treatment course
4 consecutive days; day-5 assessment
Vehicle
10% DMSO/90% acetone
Study groups and reported outcomes
Group / doseComparatorObserved resultReference
Affected left-ear application
3% BMS-509744		IMQ/vehicle and normal groups; right-ear application; separate prednisolone comparatorReduced affected-ear thickening versus IMQ/vehicle (p < 0.05, Steel test).[3]
Unaffected right-ear application
3% BMS-509744		IMQ/vehicle and affected-ear applicationNo significant reduction of affected left-ear thickening versus IMQ/vehicle.[3]
Affected left-ear application
Model: 7–8-week-old female BALB/c mice with topical imiquimod-induced left-ear psoriasis-like inflammation
Route: Topical, left ear
Frequency: Once daily, 1 h before imiquimod
Reported limits: Application volume and mass per ear are not specified in the adopted main-text regimen.
Unaffected right-ear application
Model: 7–8-week-old female BALB/c mice with topical imiquimod-induced left-ear psoriasis-like inflammation
Route: Topical, right ear
Frequency: Once daily, 1 h before left-ear imiquimod
Reported limits: Application volume and mass per ear are not specified in the adopted main-text regimen.
Methods and source locations

Compound reported in the paper: BMS-509744; Compound label in the paper: BMS-509744

Results concern the material and conditions tested by the authors; no salt conversion or catalog-lot performance claim.

Materials and Methods: Compound and IMQ-Induced Psoriasis-Like Skin Inflammation; Results: Topical Application of BMS-509744 to the Skin of the IMQ-untreated Right Ear did Not Ameliorate Dermatitis; Figure 5 and caption; Discussion.

Day-5 affected left-ear thickening: Micrometer; Steel test; Figure 5 and caption — Materials and Methods: Compound and IMQ-Induced Psoriasis-Like Skin Inflammation; Results: Topical Application of BMS-509744 to the Skin of the IMQ-untreated Right Ear did Not Ameliorate Dermatitis; Figure 5 and caption; Discussion.

Affected left-ear application · Materials and Methods: Compound and IMQ-Induced Psoriasis-Like Skin Inflammation; Results: Topical Application of BMS-509744 to the Skin of the IMQ-untreated Right Ear did Not Ameliorate Dermatitis; Figure 5 and caption; Discussion.

Unaffected right-ear application · Materials and Methods: Compound and IMQ-Induced Psoriasis-Like Skin Inflammation; Results: Topical Application of BMS-509744 to the Skin of the IMQ-untreated Right Ear did Not Ameliorate Dermatitis; Figure 5 and caption; Discussion.

Specifications

Manufacturer Adooq Bioscience
Actions Inhibitor
CAS Number 439575-02-7
Applications Itk Inhibitor
Formula C32H41N5O4S2
Molecular Weight 623.8
SMILES
CC1=C(C=C(C(=C1)OC)C(=O)N2CCN(CC2)C(=O)C)SC3=CN=C(S3)NC(=O)C4=CC=C(C=C4)CNC(C)C(C)(C)C

Storage & Solubility

In Vitro Solubility

Reported Solubility

No reported solubility data are available for this product.

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] Zhong Y, Dong S, Strattan E, et al. Targeting interleukin-2-inducible T-cell kinase (ITK) and resting lymphocyte kinase (RLK) using a novel covalent inhibitor PRN694. The Journal of biological chemistry (2015). PMID: 25593320 DOI: 10.1074/jbc.m114.614891 Source material
  2. [2] Dondorf S, Schrader A, Herling M. Interleukin-2-inducible T-cell kinase (ITK) targeting by BMS-509744 does not affect cell viability in T-cell prolymphocytic leukemia (T-PLL). The Journal of biological chemistry (2015). PMID: 25888568 DOI: 10.1074/jbc.l115.644641 Source material
  3. [3] Otake S, Otsubaki T, Uesato N, et al. Topical Application of BMS-509744, a Selective Inhibitor of Interleukin-2-Inducible T Cell Kinase, Ameliorates Imiquimod-Induced Skin Inflammation in Mice. Biological & pharmaceutical bulletin (2021). PMID: 33473072 DOI: 10.1248/bpb.b20-00850 Source material

Publications

2 publications citing this product

  1. Samson AA, .et al. , Methods Mol Biol, 2017, 1571:221-232 PMID: 28281259
  2. YK Tak, .et al. , Anal. Chem., 2013, 85 (9), pp 4273-4278 PMID: 23573871

Added to your cart

View Cart Checkout
Loading...