Torkinib (PP242) - Moligand™, 10mM in DMSO , Inhibitor of mechanistic target of rapamycin kinase;Inhibitor of PAS domain containing serine/threonine kinase, CAS No.1092351-67-1, Inhibitor of mechanistic target of rapamycin kinase;Inhibitor of PAS domain containing serine/threonine kinase

CAS: 1092351-67-1 Cat. No.: T409136 Summenformel: C₁₆H₁₆N₆O Molekulargewicht: 308.34

GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

2-(4-amino-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Übersicht

Information

Torkinib (PP242) Torkinib (PP242) is a selective mTOR inhibitor with IC50 of 8 nM in cell-free assays; targets both mTOR complexes with >10- and 100-fold selectivity for mTOR than PI3Kδ or PI3Kα/β/γ, respectively. Torkinib (PP242) induces mitophagy and
In vitro

PP242 exhibits potent selectivity for mTOR over other PI3K family kinases such as p110α, p110β, p110γ, p110δ, and DNA-PK with IC50 of 1.96 μM, 2.2 μM, 1.27 μM, 0.102 μM, and 0.408 μM, respectively. PP242 displays some inhibitory activity against Ret, PKCα, PKCβ, and JAK2, while exhibits remarkable selectivity against 215 other protein kinases. Unlike rapamycin, PP242 inhibits both mTORC1 and mTORC2. In BT549 cells, PP242 treatment (0.04-10 μM) inhibits the phosphorylation of Akt, the mTOR substrate p70S6K, and its downstream target S6 in a dose-dependent manner. PP242 potently inhibits PKCα with IC50 of 49 nM. Low concentrations of PP242 inhibit the phosphorylation of Akt S473 and higher concentrations partially inhibit Akt T308-P in addition to S473-P. As PP242 is a more effective mTORC1 inhibitor than rapamycin, PP242 inhibits the proliferation of primary MEFs, and the phosphorylation of 4EBP1 at T36/45 and S65, more potently than rapamycin. PP242 but not rapamycin potently inhibits cap-dependent translation, by causing a higher level of binding between 4EBP1 and eIF4E than rapamycin. PP242 potently inhibits the proliferation of p190-transformed murine BM, SUP-B15, and K562 cells with GI50 of 12 nM, 90 nM, and 85 nM, respectively. PP242 also inhibits the growth of solid tumor cell lines such as SKOV3, PC3, 786-O, and U87 with GI50 of 0.49 μM, 0.19 μM, 2.13 μM, and 1.57 μM, respectively. PP242 is also more effective than rapamycin in achieving cytoreduction and apoptosis in multiple myeloma (MM) cells.

In vivo

Administration of PP242 is able to completely inhibit the phosphorylation of Akt at S473 and T308 in fat and liver of mice. PP242 only partially inhibits the phosphorylation of Akt in skeletal muscle and is more effective at inhibiting the phosphorylation of T308 than S473, despite able to fully inhibit the phosphorylation of 4EBP1 and S6. Oral administration PP242 potently delays the leukemia onset in the mice model, and induces leukemia regression by inhibiting mTORC2 and mTORC1 activation that correlates with loss in cell size. PP242 treatment potently inhibits the growth of 8226 cells in mice.
Cell Data

cell lines：Different tumor cell lines including NCI-H460, MDA-MB231, MES-SA, NCI-H460 PTX, MDA-MB-231 PTX, MES-SA Dx5, and HCT-15.

Concentrations：Dissolved in DMSO, final concentrations ~10 μM

Incubation Time：72 hours

Powder Purity:≥97%

Specifications

Synonyme

2-(4-amino-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol

Spezifikationen & Reinheit

Moligand™, 10mM in DMSO

Biochemische und physiologische Mechanismen

Torkinib (PP242) is a selective mTOR inhibitor with IC50 of 8 nM in cell-free assays; targets both mTOR complexes with >10- and 100-fold selectivity for mTOR than PI3Kδ or PI3Kα/β/γ, respectively. Torkinib (PP242) induces mitophagy and apoptosis.

Storage

Store at -80°C

Verschickt in

Dry ice packs + Cold packs

Dieses Produkt erfordert Kühlkettenversand. Grundversand und andere Economy-Optionen sind nicht verfügbar.

Note

Moligand™

Aktionsart

INHIBITOR

Mechanismus der Wirkung

Inhibitor of mechanistic target of rapamycin kinase;Inhibitor of PAS domain containing serine/threonine kinase

Namen und Kennungen

Isomere SMILES

CC(C)N1C2=NC=NC(=C2C(=N1)C3=CC4=C(N3)C=CC(=C4)O)N

Molekulargewicht

308.34

Reaxy-Rn

11730137

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=11730137&ln=

Zugehörige Ziele (menschlich)

RET Tclin Proto-oncogene tyrosine-protein kinase receptor Ret (2 Activities)

Discover Target: RET

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

PIP5K1C Tchem Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (1 Activities)

Discover Target: PIP5K1C

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

PRKCE Tchem Protein kinase C epsilon type (1 Activities)

Discover Target: PRKCE

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

MAP3K19 Tchem Mitogen-activated protein kinase kinase kinase 19 (1 Activities)

Discover Target: MAP3K19

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

BMPR1B Tchem Bone morphogenetic protein receptor type-1B (1 Activities)

Discover Target: BMPR1B

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

BRSK1 Tchem Serine/threonine-protein kinase BRSK1 (1 Activities)

Discover Target: BRSK1

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

ACVR2A Tchem Activin receptor type-2A (1 Activities)

Discover Target: ACVR2A

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

ACVR2B Tchem Activin receptor type-2B (1 Activities)

Discover Target: ACVR2B

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

ACVR1 Tchem Activin receptor type-1 (1 Activities)

Discover Target: ACVR1

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

ACVRL1 Tchem Serine/threonine-protein kinase receptor R3 (1 Activities)

Discover Target: ACVRL1

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

JAK2 Tclin Tyrosine-protein kinase JAK2 (1 Activities)

Discover Target: JAK2

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

MAP2K5 Tchem Dual specificity mitogen-activated protein kinase kinase 5 (1 Activities)

Discover Target: MAP2K5

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

MTOR Tclin Serine/threonine-protein kinase mTOR (6 Activities)

Discover Target: MTOR

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

Application Protocols

Only manufacturer-verified protocols and recommended conditions are listed here. For this SKU, validated application protocols are not specified.

• Tested applications: Not specified for this item; refer to CoA/Spec Sheet.
• Recommended concentrations/dilutions: Not specified for this item; refer to CoA/Spec Sheet.

General reminder: End users should optimize assay conditions (vehicle percentage, dosing regimen, exposure time, and readouts) empirically for their specific system.

Biological Roles

Research context (literature/general; for research use only):

• Torkinib (PP242) is widely cited as an ATP-competitive inhibitor of the mechanistic target of rapamycin (mTOR) kinase and has been used to interrogate both mTORC1 and mTORC2 signaling in biochemical and cellular systems. Unlike allosteric rapalogs that primarily modulate mTORC1, PP242 has been reported to inhibit phosphorylation events downstream of both complexes in many cell systems.

Pathway and readouts (typical biochemical markers):

• Downstream mTORC1 markers: decreased phosphorylation of S6K and 4E-BP1 is commonly monitored.
• Downstream mTORC2 marker: decreased phosphorylation of Akt (Ser473) is often used as a functional readout for mTORC2 inhibition.

Use cases in chemical biology (examples):

• Time-course studies dissecting acute vs. chronic mTOR inhibition.
• Comparative profiling with PI3K inhibitors to parse pathway cross-talk.
• Target-validation experiments and probe development as a reference inhibitor in kinase panels.

Important notes:

• Potency, selectivity, and cellular efficacy can vary by cell type, assay conditions, and protein expression levels; researchers should calibrate dosing regimens and exposure times empirically.
• No medical or clinical uses are claimed or supported; this product is provided strictly for laboratory research.

Buffer Applications

This item is a discrete small-molecule inhibitor and is not a buffering agent. Buffer formulation guidance is therefore not directly applicable.

Practical note (general): If preparing assay solutions, dilute DMSO stocks into pre-equilibrated assay buffer (e.g., HEPES-, Tris-, or phosphate-based buffers) with vigorous mixing to mitigate precipitation. Validate final DMSO percentage and buffer composition for your specific biological system.

Green Alternatives

Green chemistry comparison is not typically applicable to this product because it is a discrete bioactive small molecule, not a solvent or bulk reagent with interchangeable options.

• If your workflow involves large volumes of organic solvents (e.g., for stock solutions or purification), consider greener solvent choices and practices around this compound:
  • Prefer ethanol or isopropanol over chlorinated solvents where assay compatibility allows (general guidance).
  • Minimize DMSO waste through concentrated master stocks and aliquoting to reduce freeze–thaw cycles and discard.
  • Employ microscale purification and analysis (e.g., analytical SFC or UPLC) to reduce solvent consumption.

Note: There is no “green substitute” for the active compound itself since its bioactivity is structure-specific.

Pharmaceutical Uses

This product is supplied for laboratory research only and is not an excipient, API, or GMP material.

• Intended role: reference inhibitor for discovery research, target validation, and method development in non-clinical settings.
• Pharmacopeial status: Not specified for this item; refer to CoA/Spec Sheet. There is no indication of compendial compliance (USP/EP/JP) for this SKU.

Formulation/context in research (general):

• In preclinical labs, small-molecule tool compounds are often formulated as DMSO stocks for in vitro assays or as vehicle-dosed solutions for exploratory in vivo studies under approved protocols; any such use must be determined and validated by the end user. No formulation guidance is provided or implied for this specific item.

Regulatory note:

• No therapeutic claims are made. This material is not for human or veterinary use, not for diagnostic procedures, and not for use in foods or cosmetics.

Physical Properties

Item-specific physicochemical specifications have not been provided.

• 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 for typical solid small-molecule tool compounds; if required, refer to literature or DSC/TGA data (not provided for this item).
• Density: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility: Not specified for this item; refer to CoA/Spec Sheet.
• logP/logD: Not specified for this item; refer to CoA/Spec Sheet.
• pKa(s): Not specified for this item; refer to CoA/Spec Sheet.
• Refractive index/UV cutoff: Not applicable for solids; Not specified for this item; refer to CoA/Spec Sheet.

Practical notes (general research guidance, not item-specific):

• Kinase inhibitors of this class are commonly prepared as concentrated DMSO stocks for biochemical assays and cell-based studies; actual solubility limits vary by batch, salt form, and polymorph. Perform a small-scale solubility screen (DMSO, DMF, ethanol, co-solvent with aqueous buffers) if method development is needed.
• Hygroscopicity and polymorphism can influence apparent melting range and dissolution rate; verify with the lot-specific CoA if these attributes are critical to your workflow.

Quality and Grades

• Grade/Purity: Moligand™

What Moligand™ signifies (program context, general description):

• Moligand™ denotes inclusion in a curated small-molecule/ligand library for chemical biology and screening. Emphasis is typically placed on identity confirmation and suitability for target engagement studies rather than chromatographic solvent specifications.

Item-specific quality notes:

• Identity, purity, and form (free base vs. salt, solvate content, polymorph) are critical for reproducible bioassay results. For this SKU, itemized purity percentage, residual solvent limits, water content, and counterion are not specified for this item; refer to CoA/Spec Sheet.

Analytical verification (recommended user checks):

• Confirm structure and purity as needed by NMR, LC–MS (or HRMS), and HPLC/UPLC purity in your receiving lab if your application is sensitive to minor impurities.
• If quantitative work is planned (e.g., IC50, Ki, or target occupancy), consider preparing a secondary in-house reference solution from freshly opened material and verifying concentration by quantitative NMR or UV where appropriate (after verifying extinction coefficient).

Stabilizers/inhibitors:

• None are disclosed for this item; Not specified for this item; refer to CoA/Spec Sheet.

Reaction and Applications

This compound is supplied as a finished small-molecule research tool and is not typically employed as a reagent or catalyst in synthetic transformations.

• Chemical reaction use: Not generally applicable. It is not commonly used as a substrate, coupling partner, or catalyst in preparative organic chemistry.
• If synthetic derivatization is desired (e.g., probe development), standard medicinal chemistry tactics (amide coupling, N-alkylation, or linker installation) may apply depending on the functional groups present in the specific structure of PP242; consult primary structural data and perform feasibility assessments.

For research usage, see the “Biological Roles” section which is more relevant to this product’s application space.

Reaction Conditions

This section is not typically applicable: the product is used as a finished research tool compound, not as a reagent in chemical reactions.

• If chemical modification is planned for probe synthesis, select conditions compatible with the verified functional groups in PP242 and confirm stability by LC–MS. Protect labile motifs if necessary and avoid harsh acidic/oxidative conditions until compatibility is established.

There are no item-specific reaction condition recommendations for this SKU.

Safety and Handling

Hazard classification for this specific item is not provided.

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

General laboratory safety guidance (not a substitute for the SDS):

• Handle in a chemical fume hood, avoiding inhalation of dust or aerosols. Wear appropriate PPE: lab coat, safety glasses, and disposable nitrile gloves. For weighing fine powders, consider a balance enclosure.
• Avoid contact with oxidizers and strong acids/bases unless compatibility has been assessed. Prevent release to environment; collect waste in properly labeled organic waste containers per institutional guidelines.
• First aid (general): In case of skin or eye contact, rinse with copious water for at least 15 minutes and seek medical attention if irritation persists. If inhaled, move to fresh air; if ingested, do not induce vomiting—seek medical attention.
• Thermal stability: Avoid prolonged exposure to elevated temperatures; follow storage guidance below to maintain integrity.
• Transport and spill response: Shipments arrive on dry ice/cold packs. For small spills, avoid dust generation; sweep with minimal agitation and dispose of as hazardous waste.

Always consult the item-specific SDS for authoritative hazard, toxicological, and disposal information.

Solvent Selection

This product is a research-grade small-molecule tool. Solvent choice is typically driven by assay format and required concentration.

General solvent guidance for hydrophobic kinase inhibitors (literature/general):

• Primary stock solvent: DMSO is commonly used due to high solvating power and compatibility with biochemical and cell-based assays at low final percentages (e.g., ≤0.1–0.5% v/v).
• Co-solvent strategies: For aqueous assays, dilute DMSO stocks into buffer slowly with vigorous mixing to minimize precipitation. If needed, include co-solvents like ethanol or PEG-400 at low levels consistent with assay tolerance.
• Alternative organic media: DMF and NMP can dissolve challenging solids but may be less biocompatible; use sparingly and validate against assay controls.

Considerations when choosing among solvents:

• Purity and water content of the solvent can influence compound stability. Use anhydrous, inhibitor-free solvents for long-term stock solutions if the compound is moisture- or base-sensitive (confirm via CoA/SDS/literature).
• Adsorptive losses: Highly lipophilic compounds can adsorb to plastics. Prefer glass vials for stock preparation and storage; low-bind plastics may mitigate losses in high-throughput settings.

Note: Item-specific solubility limits and solvent compatibility are not specified for this item; refer to CoA/Spec Sheet or perform a small solubility screen.

Storage and Reconstitution

• Storage conditions (item-specific): Store at -80°C.
• Shipped in (item-specific): Dry ice packs + Cold packs.

Handling and stability notes:

• Maintain the cold chain upon receipt. Before opening, allow the sealed container to equilibrate to room temperature in a desiccated environment to minimize condensation on the material.
• Aliquoting is recommended to avoid repeated freeze–thaw and to maintain consistency across experiments.

Reconstitution:

• Reconstitution solvent, concentration, and stability are not specified for this item; refer to CoA/Spec Sheet. If method development is required, users commonly evaluate DMSO for initial stock preparation and assess stability by LC–MS/HPLC under intended storage conditions.

Short-term storage of solutions (general guidance):

• For assay stocks prepared by the user, store tightly sealed, protected from light and moisture, and minimize headspace. Validate freeze–thaw stability and adsorption to container materials experimentally for your application.

Always consult the lot-specific CoA and SDS for authoritative guidance.

Structure and Identity

This product is the research tool compound Torkinib (PP242), a small-molecule inhibitor supplied for screening and chemical biology.

• Product name: Torkinib (PP242)
• CAS: 1092351-67-1
• CID: 135565635
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.

Structural features (general knowledge for PP242, not item-specific):

• PP242 is widely described in the literature as an ATP-competitive inhibitor targeting the mTOR kinase domain. Detailed 2D structural descriptors (rings, heteroatoms, substituent pattern) should be confirmed directly from a primary database (e.g., CoA, PubChem) for the exact batch supplied.

2D structure in words (literature/general):

• The scaffold reported for PP242 comprises a drug-like heteroatom-containing framework consistent with mTOR ATP-site binders; confirm exact functional group topology via an authenticated structure file for the lot supplied.

Synthetic Utility

As supplied, Torkinib (PP242) is a final bioactive small molecule rather than a synthetic building block.

• Utility in synthesis: Not typically used as a reagent, catalyst, or common intermediate.
• Derivatization: If analog or probe synthesis is desired, the feasibility depends on the exact functional groups and substitution pattern of PP242 (confirm via structure files). Medicinal chemistry modifications might target positions that tolerate substitution without abrogating mTOR binding; such strategies should be guided by SAR reported in the literature and docking/biophysical validation.

For most users, the relevant value of this product lies in its role as a reference standard in biochemical assays rather than as a starting material for synthetic campaigns.

Target Specificity

Only product-data–derived, experimentally verified target details may be listed here. For this SKU, target specificity parameters are not specified.

• Target/epitope: Not specified for this item; refer to CoA/Spec Sheet.
• Species/clone/isotype (if applicable): Not applicable.

Note: While PP242 is widely discussed in the literature in the context of mTOR pathway research, item-specific validated specificity data are not provided here.