NVP-ADW742 - 10mM in DMSO , CAS No.475488-23-4

CAS: 475488-23-4 Cat. No.: N408780 Formula: C₂₈H₃₁N₅O Peso molecolare: 453.58

GRADE & PURITY 10mM in DMSO

Synonyms

GSK 552602A, ADW742 | 5-(3-(benzyloxy)phenyl)-7-((1r,3r)-3-(pyrrolidin-1-ylmethyl)cyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Panoramica

Information

NVP-ADW742 NVP-ADW742 (GSK 552602A) is an IGF-1R inhibitor with IC50 of 0.17 μM, >16-fold more potent against IGF-1R than InsR; little activity to HER2, PDGFR, VEGFR-2, Bcr-Abl and c-Kit.
In vitro

NVP-ADW742 exhibits a 6-fold greater selectivity for IGF-1R versus InsR with IC50 of 2.8 μM; minimal inhibitory activity against c-Kit, HER1, PDGFR, VEGFR2, or Bcr-Abl p210 with IC50 greater than 5 μM. NVP-ADW742 significantly inhibits the serum-stimulated cell proliferation in a variety of tumor cell lines in dose-dependent manner, with IC50 values of 0.1-0.5 μM for the multiple myeloma (MM) cell lines, and the antitumor effects on MM cells can not be overcome by the co-culture with BMSCs. NVP-ADW742 also abrogates the responsiveness of tumor cells to IL-6 in the presence of serum. In addition, NVP-ADW742 is active against MM cell lines with resistance to conventional (cytotoxic chemotherapy, dexamethasone) or investigational (thalidomide, CC-5013, TRAIL/Apo2L, PS-341) anticancer agents, as well as primary tumor cells from MM patients with multi-drug-resistant disease. NVP-ADW742 decreases the production of VEGF by tumor cells and bone marrow stromal cells, and suppresses the IGF-1-induced secretion of VEGF by various tumor types such as thyroid cancer cells or MM cells. IGF-1R inhibition by NVP-ADW742 (0.75 μM) sensitizes MM cells or prostate cancer cells to other anticancer agents such as doxorubicin, melphalan, dexamethasone, TRAIL/Apo2L, or PS-341.

In vivo

Administration of NVP-ADW742 at 10 mg/kg twice daily significantly inhibits tumor growth, prolongs survival, and enhances the antitumor effect of cytotoxic chemotherapy melphalan in the mice model of diffuse MM.
Cell Data

cell lines：

Concentrations：Dissolved in DMSO, final concentrations ~ 10 μM

Incubation Time：48 hours

Powder Purity:≥96%

Specifications

Sinonimi

GSK 552602A, ADW742 | 5-(3-(benzyloxy)phenyl)-7-((1r,3r)-3-(pyrrolidin-1-ylmethyl)cyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Specifiche e purezza

10mM in DMSO

Meccanismi biochimici e fisiologici

NVP-ADW742 (GSK 552602A) is an IGF-1R inhibitor with IC50 of 0.17 μM, >16-fold more potent against IGF-1R than InsR; little activity to HER2, PDGFR, VEGFR-2, Bcr-Abl and c-Kit.

Condizioni di conservazione di stoccaggio

Store at -80°C

Spedito in

Dry ice packs + Cold packs

Questo prodotto richiede spedizione a catena fredda. I servizi di terra e altri servizi economici non sono disponibili.

Nomi e identificatori

Isomeri SMILES

C1CCN(C1)CC2CC(C2)N3C=C(C4=C(N=CN=C43)N)C5=CC(=CC=C5)OCC6=CC=CC=C6

Peso molecolare

453.58

Reaxy-Rn

20351333

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=20351333&ln=

Obiettivi associati (umani)

FLT3 Tclin Receptor-type tyrosine-protein kinase FLT3 (1 Activities)

Discover Target: FLT3

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

Application Protocols

No tested application protocols (e.g., WB, IHC, IF, enzymatic assay setups, or cell-based dosing instructions) are provided in the product data for this item.

General research-use guidance

• Prepare concentrated DMSO stocks when solubility allows; dilute into assay medium immediately before use with consistent vehicle control.
• Establish a concentration–response curve over several logs, using appropriate positive/negative controls.
• Record lot number, stock concentration, solvent, and preparation date in your ELN/LIMS.

For detailed protocols, follow your institutional SOPs or peer-reviewed methods relevant to your assay system. This product is supplied strictly for research use only.

Biological Roles

General literature context (for the chemical entity associated with CAS 475488-23-4; verify details against primary sources before experimental use):

• NVP-ADW742 is reported in the literature as a small-molecule kinase-tool compound designed to probe insulin-like growth factor signaling by inhibiting IGF-1 receptor (IGF-1R) catalytic activity. Such tool compounds are used to interrogate pathway dependence in cellular models and to study receptor-mediated signaling cascades in vitro.
• Typical readouts in discovery biology include phosphorylation status of downstream effectors (e.g., AKT/ERK), changes in reporter gene activity, or modulation of proliferation under ligand stimulation. Assay conditions, potencies, and selectivity profiles are experiment-dependent and should be sourced from peer-reviewed publications or internal validation.
• When deploying any bioactive tool, implement orthogonal target-engagement assays (e.g., CETSA, NanoBRET, or biochemical enzyme assays) and confirm selectivity against related kinases to deconvolute on-target versus off-target effects.
• Solvent considerations: maintain low final DMSO concentrations (often ≤0.1–1% v/v) in cellular systems to limit solvent artifacts. Include DMSO-matched vehicle controls and, if feasible, a structurally unrelated comparator with similar nominal target.

Important: The above describes literature-reported biological roles for the named chemical entity and does not constitute product-specific specifications or claims. Use strictly for research; no medical or clinical use is intended.

Buffer Applications

This product is a discrete small-molecule research compound, not a buffering agent. Therefore, standard buffer system guidance (pKa ranges, buffer recipes) is not directly applicable.

Practical notes for assay buffers (general)

• When diluting DMSO stocks into aqueous assay buffers, maintain consistent DMSO across all wells/tubes (commonly ≤0.1–1% v/v) and include vehicle controls.
• Add compound last to pre-equilibrated buffer containing protein/serum components to minimize precipitation. Brief vortexing or plate shaking helps achieve homogeneity.
• If adsorption losses are suspected, consider adding a low level of nonionic surfactant (e.g., 0.01–0.05% Tween-20) subject to assay compatibility.

For actual buffer preparation details (pH, ionic strength, components), follow your assay SOPs; this product does not function as a buffering agent.

Green Alternatives

Because this listing represents a discrete small-molecule research compound rather than a bulk solvent or common reagent, traditional “green substitution” analysis is not typically applicable.

• Solvent choice considerations (general): If you formulate stocks or run extractions, prefer lower-toxicity, higher-boiling, and recyclable solvents. For example, replacing DMF with ethanol or water/DMSO mixtures where assay-compatible can improve EHS profiles.
• Waste minimization: Use miniaturized assay formats (e.g., 384/1536-well) and compound plating to reduce solvent consumption and chemical waste.
• Energy usage: Store only the aliquot volume you need at ultra-low temperatures; keep working stocks at –20 °C when compatible to reduce freezer load—validate stability before changing storage.

If you have process-scale needs (e.g., analog synthesis), consult green chemistry metrics (E-factor, PMI) and solvent selection guides (GSK/ACS) for route development. For this catalog item itself, there is no greener “drop-in” replacement because it is a specific structure used for research probing.

Pharmaceutical Uses

This catalog item is supplied strictly for research use only. No medical, diagnostic, or therapeutic use is intended or permitted.

• Excipient/formulation status: Not applicable; this is not an excipient or approved pharmaceutical ingredient.
• Pharmacopoeial monographs: None indicated in the product data.
• Manufacturing relevance: In drug discovery labs, compounds of this type may be used as reference standards or tool molecules in preclinical research assays. Such activities are non-clinical and outside regulated GMP manufacturing unless otherwise specified by your quality system.

Any discussion of dosage forms, clinical applications, or therapeutic claims is out of scope and not provided.

Physical Properties

Item-specific physical constants are not provided in the product data.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point: Not specified for this item; refer to CoA/Spec Sheet.
• Boiling point: Not applicable/rarely reported for bioactive solids; Not specified for this item; refer to CoA/Spec Sheet.
• Density: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility: Not specified for this item; refer to CoA/Spec Sheet.
• logP/logD, pKa: Not specified for this item; refer to CoA/Spec Sheet.
• Refractive index/UV cutoff: Not specified for this item; refer to CoA/Spec Sheet.

General guidance (literature/practice, not item-specific)

• Many kinase-tool molecules are prepared as concentrated stock solutions in anhydrous DMSO for screening use, then diluted into assay buffers immediately before use to minimize precipitation and adsorption losses.
• If you retrieve literature properties for this CAS/CID (e.g., approximate solubility in DMSO, pKa), confirm experimentally in your assay matrix because protein, salt, and cosolvent content strongly influence apparent solubility and recovery.
• For spectroscopic QC, LC–MS-compatible mobile phases and short gradients (2–10 min) are commonly adequate to verify purity and identity of small-molecule libraries. Always use the CoA for acceptance criteria.

Quality and Grades

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.

How to interpret grade and documentation (general guidance)

• For small-molecule screening libraries, typical acceptance criteria include LC–MS purity (area %) and verified molecular mass; some labs also require NMR identity checks. When present, these criteria are detailed in the item’s CoA.
• If “HPLC grade” or “bioactive screening grade” is specified on the CoA, it usually indicates low-level UV-active impurities and suitability for biochemical assays; however, exact thresholds (e.g., ≥95% peak area) are defined by the supplier’s specification—always check the CoA.
• Stabilizers, salt forms, and residual solvent limits, when applicable, will be called out in the specification. Absence of such information in the product data means you should confirm on the CoA before use in regulated or high-sensitivity applications.

Recommendations

• Document the lot number and retain a copy of the CoA in your ELN/LIMS.
• If your workflow is sensitive to counterions or residual solvents, perform a quick orthogonal check (qNMR, Karl Fischer, headspace GC) on receipt.

Reaction and Applications

This product is categorized as a small-molecule entry in a screening/compound library and is not typically employed as a synthetic reagent or catalyst.

• Synthetic reactions: Not typically applicable. No manufacturer-supplied use cases beyond research screening are provided.
• Assay context (general, literature/practice): Small-molecule tool compounds are commonly used in biochemical or cell-based assays to probe signaling pathways, target engagement, and structure–activity relationships. When using such compounds, confirm identity and purity by LC–MS and establish dose–response curves with appropriate controls.
• Plate handling: Pre-dispense DMSO stocks into 96/384-well plates under dry conditions; seal to prevent solvent evaporation and water uptake.
• Controls: Include vehicle controls (DMSO-matched), positive/negative controls, and, when possible, orthogonal assays to validate on-target activity.

Manufacturer Applications: Not specified for this item; refer to catalog/CoA.

Note: No medical or clinical claims are made or implied. Use is limited to research applications only, as indicated by the product’s Research Use Note.

Reaction Conditions

Not typically applicable. NVP-ADW742 is listed as a small-molecule tool compound for research screening rather than a reagent used to mediate or catalyze chemical reactions.

If you are performing chemical modifications of this scaffold (custom research):

• Solvents: choose based on actual functional groups (e.g., polar aprotic for SNAr on heteroaromatics; alcoholic or aqueous media for salt exchanges). Verify stability in the chosen medium.
• Temperatures: keep within stability limits determined by DSC/TGA or stress testing; absent item-specific data, start with ambient conditions and escalate cautiously.
• Atmosphere: use inert atmosphere when performing moisture/oxygen-sensitive steps.
• Workup/purification: reversed-phase prep HPLC is common for polar, heteroaromatic drug-like molecules; normal-phase silica can lead to adsorption or tailing—test at small scale first.

These are general chemistry considerations and not specifications for this item.

Safety and Handling

Safety information specific to this item is not provided in the product data.

• GHS classification: Not specified for this item; refer to SDS.
• Signal word / pictograms / H-statements: Not specified for this item; refer to SDS.

General laboratory safety (good practice; defer to SDS/PI)

• Handle in a fume hood or ventilated enclosure; avoid inhalation of dust/aerosols and skin/eye contact.
• Wear appropriate PPE: lab coat, safety glasses, and chemical-resistant gloves (e.g., nitrile). Change gloves frequently when handling DMSO solutions.
• Avoid mixing with strong oxidizers and strong acids/bases unless procedure dictates and hazards are reviewed.
• In case of exposure: rinse affected area with water for 15 minutes; remove contaminated clothing; seek medical advice. If inhaled, move to fresh air. If ingested, do not induce vomiting; seek medical attention.
• Waste disposal: collect solutions and contaminated disposables as halogen-free organic waste unless your local EHS dictates otherwise.
• Transport/stability: This item is shipped on dry ice + cold packs and labeled for –80°C storage; minimize freeze–thaw cycling of aliquots.

Always consult the SDS for authoritative hazard classifications, first aid, firefighting measures, accidental release measures, and incompatibilities.

Solvent Selection

Item-specific solubility data are not provided. The notes below are general, literature/practice-based guidance for small-molecule screening compounds and should be verified experimentally for NVP-ADW742.

• Primary stock solvent (typical): anhydrous DMSO due to broad solvating power and compatibility with biochemical assays.
• Cosolvents for assay dilution: water-based buffers with ≤1–2% DMSO, optionally with 0.01–0.1% nonionic surfactant (e.g., Tween-20 or Pluronic F-127) to mitigate adsorption losses—verify assay tolerance.
• Alternative solvents: DMF or ethanol can be used for intermediate stocks; avoid high ethanol content in enzyme assays when possible.
• Adsorption and precipitation: low-solubility compounds often benefit from polypropylene labware and immediate dilution into warm buffer with vigorous mixing.

Quick comparison (general)

• DMSO: highest solvency, excellent chemical stability; may affect enzyme kinetics above 1–2% v/v.
• DMF: similar solvency; higher toxicity and less assay-friendly.
• Ethanol: greener; lower solvency for many heteroaromatics; assay tolerance typically ≤1% v/v.

Practical tips

• Prepare small aliquots (e.g., 5–50 µL) at a convenient stock concentration (1–50 mM as solubility allows). Minimize freeze–thaw cycles.
• Filter sterilization is generally unnecessary for chemical stock solutions; if required, use PTFE syringe filters and confirm no adsorption losses.

Storage and Reconstitution

Storage and shipping (item-specific)

• Storage conditions: Store at –80 °C.
• Shipped in: Dry ice packs + Cold packs.

Stability and handling (general guidance; not item-specific specifications)

• Upon receipt, allow the container to equilibrate to room temperature in a desiccated environment before opening to minimize moisture condensation.
• If solution stocks are prepared (e.g., in anhydrous DMSO), dispense into single-use aliquots to avoid repeated freeze–thaw cycles and adsorption to vial walls. Clearly label solvent, concentration, and date.
• Protect from light if your internal characterization indicates photolability; use amber vials or foil wrapping as appropriate.

Reconstitution

• Reconstitution solvent, concentration, and expected solubility: Not specified for this item; refer to CoA/Spec Sheet and verify experimentally.
• If insolubility is encountered, warm gently (e.g., 25–37 °C) and vortex/sonicate briefly. Do not heat above the compound’s known stability limits.

Always refer to the product’s CoA and SDS for definitive storage/stability guidance and to your laboratory SOPs for handling and disposal. Research use only.

Structure and Identity

Brief overview of a research-only small molecule listed in our small-molecule libraries.

• Product name: NVP-ADW742 (SKU: N408780)
• CAS: 475488-23-4
• PubChem CID: 9825149
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
• Structural features: Not specified for this item; refer to CoA/Spec Sheet.

Notes

• Identity confirmation should be based on the item’s CoA/Spec Sheet and, where needed, orthogonal methods (e.g., LC–MS, 1H/13C NMR, HRMS) performed in your lab.
• For cheminformatics workflows, use the provided CAS and CID to retrieve literature descriptors; verify against the CoA before use in regulated documentation.

Synthetic Utility

This product is a finished small-molecule tool compound and is not typically used as a synthetic reagent, catalyst, or building block.

• Functional-group reactivity: Not specified for this item; refer to primary literature if you intend to derivatize or conjugate the molecule.
• Derivatization: If structural modification is desired (e.g., for probe development), consult synthetic literature associated with the CAS number and plan orthogonal protection/activation strategies based on the actual functional groups present in the structure.
• Analytical controls: For any custom chemistry using this scaffold, implement LC–MS, qNMR, and, where relevant, chiral HPLC to confirm identity and purity of intermediates and final products.

In summary, the molecule serves primarily as a biological tool rather than a general synthetic reagent.

Target Specificity

Target specificity information (e.g., protein target, selectivity panel results, binding constants) is not provided in the product data for this catalog item.

• Only product-data-sourced details may be listed here. For any intended biological target information, please consult peer-reviewed literature for CAS 475488-23-4 or your internal validation reports, and document assay conditions and selectivity panels in your lab records.

No claims are made regarding target identity or selectivity for this item in this catalog entry.