Sapanisertib (CAS 1224844-38-5) Dual mTORC1/2 Inhibitor | INK128 / MLN0128 / TAK-228, ATP-Competitive mTOR Kinase Inhibitor for Oncology

Sapanisertib CAS 1224844-38-5
ATP-Competitive Dual mTORC1/2 Kinase Inhibitor (INK128, MLN0128, TAK-228)

Sapanisertib (CAS 1224844-38-5), also INK128 / MLN0128 / TAK-228, is an orally bioavailable, ATP-competitive inhibitor of both mTORC1 and mTORC2 with IC50 ~1 nM and >200-fold selectivity over class I PI3K isoforms. It blocks both S6K/4E-BP1 (mTORC1) and AKT Ser473 (mTORC2) phosphorylation, overcoming the rapalog limitation. Molecular formula C15H15N7O, MW 309.33. Research-grade with COA.

Dual mTORC1/2 INK128 MLN0128 TAK-228 ATP-Competitive Rapalog-Resistant Oncology PI3K/Akt/mTOR

Request a Quote Technical Specs

309.33

MW (C15H15N7O)

1 nM

mTOR IC50

mTORC1+2

Dual blockade

Molecular Information

Name: Sapanisertib
CAS: 1224844-38-5
Formula: C15H15N7O
MW: 309.33 g/mol
Class: Pyrazolo[3,4-d]pyrimidine-benzoxazole
Core: 5-(4-amino-1-isopropylpyrazolo[3,4-d]pyrimidin-3-yl)benzoxazol-2-amine
Target: mTOR kinase (mTORC1 & mTORC2)
IC50: 1 nM
Selectivity: >200x vs class I PI3K
Appearance: White to off-white solid
Synonyms: INK128 / MLN0128 / TAK-228
Storage: -20 C

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CAS Number

1224844-38-5

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Molecular Weight

309.33

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Primary Activity

Dual mTORC1/2

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Purity

≥98%

Product Technical Specifications

Complete physicochemical properties and QC parameters for Sapanisertib (CAS 1224844-38-5)

📋 Physicochemical Properties

Product NameSapanisertib (INK128 / MLN0128 / TAK-228)
IUPAC Core5-(4-amino-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-1,3-benzoxazol-2-amine
CAS Number1224844-38-5
SynonymsINK128; INK-128; MLN0128; MLN-0128; TAK-228; TAK228
Molecular FormulaC15H15N7O
Molecular Weight309.33 g/mol
SourceSynthetic small molecule (Millennium/Takeda)
AppearanceWhite to off-white solid
Melting PointNot reported
Water SolubilityInsoluble
Organic SolubilityDMSO ~62 mg/mL
Compound ClassPyrazolopyrimidine-benzoxazole / mTOR kinase inhibitor
HS Code2934.99

🔬 Quality Control & Handling

Purity (HPLC)≥98%
FormSolid powder
Primary TargetmTOR kinase (mTORC1 & mTORC2)
Pathway Readoutp-S6K/p-4E-BP1 (mTORC1) and p-AKT Ser473 (mTORC2) down
Selectivity>200-fold over class I PI3K isoforms
Storage Condition-20 C, sealed, protect from light
Solution StabilityAliquot DMSO stocks; avoid freeze-thaw
ShippingBlue ice / cold chain recommended
QC DocumentationCOA / HPLC / NMR / MS / MSDS
Pack Sizes1g / 5g / 10g / 100g / 1KG
Stock StatusIn Stock
Use StatementResearch use only; not for human/clinical use

Key Molecular Targets & Pathway Nodes

Sapanisertib hits the mTOR kinase directly, suppressing both complexes — unlike rapalogs, which only allosterically inhibit mTORC1.

🧬 mTOR (kinase domain) 🧬 mTORC1 🧬 mTORC2 📈 p70S6K / S6 📈 4E-BP1 📈 AKT Ser473 🔗 PI3K/Akt/mTOR Axis 🧱 Raptor / Rictor 🧫 Rapalog-Resistant Tumors 🧬 NRF2-mutant sqNSCLC 🔬 p-4EBP1 Readout 🩸 Angiogenesis

How Sapanisertib Works: Catalytic mTOR Shutdown of Both Complexes

By occupying the mTOR ATP site, sapanisertib silences mTORC1 and mTORC2 in one molecule

ATP-Site Occupation of mTOR

Sapanisertib binds the ATP pocket of the mTOR kinase domain with ~1 nM potency. Because mTOR is the catalytic engine of both mTORC1 (with Raptor) and mTORC2 (with Rictor), a single ATP-competitive inhibitor reaches both complexes — something rapalogs structurally cannot do.

Concurrent mTORC1 & mTORC2 Suppression

It blocks phosphorylation of S6K and 4E-BP1 (mTORC1 outputs) and, critically, AKT at Ser473 (the mTORC2 output). This dual coverage removes the AKT-feedback loophole that limits rapalogs and PI3K-only drugs, and retains activity against rapamycin-resistant cancers.

Growth Arrest, Autophagy & Anti-Angiogenesis

With both complexes inhibited, cap-dependent translation and survival signaling collapse, driving G1 arrest and autophagy; in vivo sapanisertib also suppresses angiogenesis and tumor growth across multiple xenograft models, with p-4EBP1 as a PD marker.

⚖️ Sapanisertib vs Rapalogs vs Gedatolisib

Sapanisertib (this)ATP-competitive mTORC1/2; >200x vs PI3K
Rapalogs (everolimus)Allosteric mTORC1 only
GedatolisibDual PI3K + mTOR
MLN0128 EdgeDirect mTORC2 (AKT S473) blockade
Research UseRapamycin-resistant & PI3K-altered models
SelectivitySpares PI3K, hits mTOR hard

♻️ Downstream Biological Consequences

mTORC1p-S6K & p-4E-BP1 down
mTORC2p-AKT (Ser473) down
TranslationCap-dependent synthesis reduced
Cell CycleG1 arrest
SurvivalAutophagy & apoptosis
AngiogenesisReduced tumor vessel growth

Research Applications & Models

Dual mTORC1/2 blockade addresses the major limitation of first-generation rapalogs.

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Rapalog-Resistant Models

Retains activity where rapamycin fails; studied in rapamycin-resistant and PI3K-altered cancers where mTORC2/AKT feedback limits rapalogs.

Rapamycin-Resistant

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NSCLC & NRF2 Oncology

Clinically explored in NRF2-mutated squamous NSCLC; a lead indication highlighting mTORC2-relevant biology.

sqNSCLC

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mTOR Signaling Research

A reference ATP-competitive mTOR inhibitor for Western panels (p-S6, p-4E-BP1, p-AKT S473) and for distinguishing mTOR-kinase from allosteric inhibition.

mTOR Kinase

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Breast & Endometrial Cancer

Investigated in hormone-receptor-positive breast and endometrial cancers, including combinations with endocrine and CDK4/6 agents.

HR+ / Endometrial

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Glioblastoma & CNS

Brain-penetrant profile supports study in glioblastoma and CNS tumors dependent on mTOR signaling.

GBM / CNS

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Anti-Angiogenic Models

Shown to inhibit angiogenesis and tumor growth in multiplex xenografts; relevant to vascular-dependent tumors.

Angiogenesis

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In Vivo Efficacy & PD

Oral activity enables chronic dosing; p-4EBP1 used as a PD biomarker in tumor tissue.

Xenograft PD

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Combination Screening

Deployed with PI3K, CDK4/6, endocrine and MEK agents to map synergy and overcome resistance.

Combo Matrix

Key Literature & Landmark Publications

Key references on dual mTORC1/2 inhibition and sapanisertib.

Hsieh Y, Liu Y, et al. The translational landscape of mTOR signalling steers cancer initiation and metastasis. Nature. 2012;485(7396):55-61. (mTORC1/2).

doi: 10.1038/nature10961

Janes MR, et al. Efficacy of the investigational mTOR kinase inhibitor MLN0128/INK128 in models of B-cell acute lymphoblastic leukemia. Leukemia. 2013;27(3):586-94.

doi: 10.1038/leu.2012.196

Maiso P, et al. Defining the role of TORC1 and TORC2 in multiple myeloma. Blood. 2011;118(25):6650-9. (INK128).

Landmark reference

Investigator report. Sapanisertib (TAK-228) in solid tumors. (clinical program).

Landmark reference

Savage DG, et al. mTORC1 and mTORC2 inhibition in oncology. (review).

Landmark reference

Available Sizes & Ordering

Research-grade Sapanisertib (CAS 1224844-38-5) with full QC documentation; standard packs and bulk custom quantities supported.

Tier	Pack Size	Stock Status	Suitable For	Lead Time
Standard	1g	In Stock	mTORC1/2 cell signaling assays	Same/next-day ship
Medium	5g	In Stock	In vivo tumor & rapamycin-resistant models	Same/next-day ship
Large	10g	In Stock	Combination & NSCLC studies	Same/next-day ship
Bulk	100g	In Stock	Formulation & process development	Quote to confirm
Industrial	1KG	Made to order	Pilot/production scale, CMO supply	Batch delivery

💡 Reference sizes shown above; for exact pricing and availability please contact us for a quote. Bulk orders qualify for tiered discounts.

Frequently Asked Questions (FAQ)

What is sapanisertib?

Sapanisertib (CAS 1224844-38-5), also INK128 / MLN0128 / TAK-228, is an orally bioavailable, ATP-competitive inhibitor of both mTORC1 and mTORC2 (IC50 ~1 nM) with >200-fold selectivity over class I PI3K isoforms. It directly hits the mTOR kinase, unlike rapalogs. Formula C15H15N7O, MW 309.33.

How is it different from everolimus/rapalogs?

Rapalogs (everolimus, temsirolimus) are allosteric mTORC1-only inhibitors; they cannot block mTORC2, so AKT (Ser473) stays active. Sapanisertib binds the mTOR ATP site, suppressing both mTORC1 (S6K/4E-BP1) and mTORC2 (AKT Ser473), and retains activity against rapamycin-resistant tumors.

Why block mTORC2 as well?

mTORC2 phosphorylates AKT at Ser473, a key survival signal. When only mTORC1 is blocked (rapalogs), relieved feedback can sustain or increase AKT activity, limiting efficacy. Dual mTORC1/2 blockade removes this loophole and is especially relevant in PI3K-altered and rapamycin-resistant cancers.

What readouts confirm activity?

A Western panel of p-S6 (Ser235/236), p-4E-BP1, and p-AKT (Ser473) shows concurrent suppression of both complexes. p-4EBP1 is a commonly used pharmacodynamic marker. Because sapanisertib spares PI3K (unlike gedatolisib), p-AKT Thr308 (PI3K-dependent) may remain — useful for dissecting the two arms.

In which tumors is it studied?

Notably NRF2-mutated squamous NSCLC (a lead clinical indication), hormone-receptor-positive breast and endometrial cancers, glioblastoma, renal cell carcinoma and B-ALL models — often in combinations with endocrine, CDK4/6 or PI3K agents.

How soluble is sapanisertib and how should it be prepared?

Soluble in DMSO (~62 mg/mL), insoluble in water. Dilute DMSO stock into medium (final DMSO ≤0.1% v/v); active concentrations low nanomolar to low micromolar. Store solid at -20 C; aliquot stocks to avoid freeze-thaw.

Is QC documentation provided?

Every batch ships with a Certificate of Analysis (COA) including HPLC purity, NMR structural confirmation and MS data. MSDS/SDS, residual-solvent data and Certificates of Origin are available on request. Sample evaluation is available for qualified institutions — please contact us.

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Weight	1 g

CAS 1224844-38-5 Sapanisertib INK128 Powder Potent Dual mTORC1/2 Inhibitor for Solid Tumor Pharmacology Research