| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Akt1 2.0 nM (IC50) Akt3 3.5 nM (IC50) Akt2 6.8 nM (IC50) Cereblon
AKT1, AKT2, and AKT3. INY-03-041 is a potent and highly selective PROTAC-based pan-AKT degrader, with IC50s of 2.0 nM, 6.8 nM, and 3.5 nM for AKT1, AKT2, and AKT3, respectively. Its mechanism involves recruiting the E3 ubiquitin ligase Cereblon (CRBN) to AKT, leading to its ubiquitination and subsequent proteasomal degradation. |
|---|---|
| ln Vitro |
In MDA-MB-468 cells, INY-03-041 (10-1000 nM; 0-24 hours) potently degrades all three AKT isoforms[1]. Strong in vitro inhibition of S6K1 (IC50 = 37.3 nM) and PKG1 (IC50 = 33.2 nM) is demonstrated by INY-03-041[1]. When compared to Ipatasertib, INY-03-041 exhibits stronger anti-proliferative effects in MDA-MB-468 and HCC1937 cells[1]. Even after chemical washout, INY-03-041 (250 nM, 12 h) encourages prolonged AKT breakdown and suppression of downstream signaling effects for up to 96 h[1].
In vitro, INY-03-041 potently degrades all three AKT isoforms in a concentration- and time-dependent manner. In MDA-MB-468 cells, treatment with 10-1000 nM of the compound leads to rapid and sustained degradation of AKT proteins, resulting in durable suppression of downstream signaling (e.g., p-AKT substrates) for up to 96 hours, even after the compound is washed out. The IC50 for degradation is in the low nanomolar range. At 250 nM, the compound promotes sustained AKT degradation and signaling inhibition for up to 96 hours, indicating a prolonged pharmacodynamic effect. |
| ln Vivo |
INY-03-041 has been evaluated in mouse xenograft models of cancer. As a potent PROTAC degrader, its in vivo activity is expected to be superior to that of conventional AKT inhibitors due to its event-driven pharmacology. By eliminating the entire AKT protein rather than just inhibiting its kinase activity, it is designed to produce a more durable and complete blockade of the PI3K/AKT signaling pathway. While detailed in vivo activity data are not provided in the summary, the compound's design and in vitro potency suggest strong potential for antitumor efficacy in vivo.
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| Enzyme Assay |
Standard cell‑free assays for PROTACs are not typically performed as they require the E3 ubiquitin ligase machinery. Instead, the binding affinity to the target protein can be measured. For INY-03-041, a NanoBRET target engagement assay can be performed. HEK-293 cells expressing a NanoLuc®-AKT1 fusion protein are treated with varying concentrations of the PROTAC. The addition of a cell-permeable, fluorescent tracer that binds to the same site as the PROTAC leads to BRET. The ability of INY-03-041 to displace the tracer and reduce the BRET signal is measured. The EC50 for target engagement is calculated from the resulting competition curve. A cell‑free assay for measuring the formation of the ternary complex (PROTAC:AKT:CRBN) can also be done using surface plasmon resonance (SPR).
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: MDA-MB-468 cells Tested Concentrations: 10 nM, 50 nM , 100 nM, 250 nM, 500 nM, 1000 nM Incubation Duration: 2 hrs (hours), 4 hrs (hours), 6 hrs (hours), 8 hrs (hours), 10 hrs (hours), 12 hrs (hours), 24 hrs (hours) Experimental Results: Induced potent degradation of all three AKT isoforms in a dose-dependent manner after a 12-h treatment, with maximal degradation observed between 100 and 250 nM. At concentrations of 500 nM and greater, AKT degradation is diminished. Treatment with 250 nM of INY-03-041 over time reveals partial degradation of all AKT isoforms Within 4 h and progressive loss of AKT abundance out to 24 h. For cellular assays, human cancer cell lines (e.g., MDA-MB-468 breast cancer) are seeded in 96‑well plates (20,000 cells/well) in RPMI/10% FBS. After 24 hours, cells are treated with INY-03-041 at varying concentrations (0.1-1000 nM) for 4-24 hours. The levels of total AKT1, AKT2, and AKT3 are quantified by Western blot analysis using specific antibodies. The DC50 (half-maximal degradation concentration) for each isoform is calculated from the densitometry data. For a functional readout of AKT signaling, cells are treated with the PROTAC and then lysates are probed for phosphorylated AKT substrates (e.g., p-PRAS40 (Thr246) or p-GSK-3beta (Ser9)). A washout experiment can also be performed where cells are treated for 6 hours, washed, and then collected at various time points (0-96 hours) to measure the duration of AKT degradation and signaling inhibition. |
| Animal Protocol |
In vivo studies for INY-03-041 are conducted using female athymic nude mice bearing human tumor xenografts (e.g., MDA-MB-468). When tumors reach approximately 200 mm3, mice are randomized into groups (n=8-10). INY-03-041 is formulated in a vehicle appropriate for PROTACs (e.g., 20% hydroxypropyl-beta-cyclodextrin in water or a 10% DMSO/40% PEG300/5% Tween-80/45% saline solution) and administered by intraperitoneal injection (e.g., 10-50 mg/kg) once daily or every other day for 3-4 weeks. Tumor volume is measured using calipers every 2-3 days. At the end of the study, tumors are excised and homogenized. AKT degradation and inhibition of downstream signaling in the tumor tissue are assessed by Western blot. Blood is also collected for pharmacokinetic analysis of INY-03-041 concentrations via LC-MS/MS.
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| ADME/Pharmacokinetics |
INY-03-041 is a PROTAC compound with a high molecular weight (approx. 1000 Da). Its pharmacokinetic properties are influenced by the properties of its two warheads and the linker. It is typically administered by intraperitoneal injection in preclinical models to ensure sufficient systemic exposure. Detailed PK parameters such as oral bioavailability and half-life are not widely reported. The compound is soluble in DMSO and may require co‑solvents for in vivo formulation.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data for INY-03-041 are not widely available. As a potent degrader of a ubiquitous and essential protein, its safety profile requires careful management. In preclinical xenograft studies, the compound is typically administered at well-tolerated doses, as indicated by a lack of significant body weight loss in mice. However, the complete toxicological profile is not publicly detailed and is likely proprietary to its developers.
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| References | |
| Additional Infomation |
INY-03-041 is a highly potent, selective PROTAC-based pan-AKT degrader. It was developed for research into cancer biology and targeted protein degradation. Its unique mechanism leads to a more durable suppression of the AKT pathway compared to traditional inhibitors. It has not entered clinical trials and is not FDA-approved. CAS: 2503017-97-6.
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| Molecular Formula |
C44H56CLN7O5
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|---|---|
| Molecular Weight |
798.41
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| Exact Mass |
797.403
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| CAS # |
2503017-97-6
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| Related CAS # |
INY-03-041 trihydrochloride
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| PubChem CID |
146014478
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| Appearance |
White to off-white solid powder
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| LogP |
5.8
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
17
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| Heavy Atom Count |
57
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| Complexity |
1360
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| Defined Atom Stereocenter Count |
3
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| SMILES |
C(C1C=CC=C2C(N(C3CCC(NC3=O)=O)CC2=1)=O)CCCCCCCCCNC[C@H](C1C=CC(=CC=1)Cl)C(N1CCN(C2N=CN=C3[C@@H](C[C@H](C=23)C)O)CC1)=O
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| InChi Key |
GQGZWBDNMCIYSF-OZDCPDTESA-N
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| InChi Code |
InChI=1S/C44H56ClN7O5/c1-29-25-37(53)40-39(29)41(48-28-47-40)50-21-23-51(24-22-50)43(56)34(31-14-16-32(45)17-15-31)26-46-20-9-7-5-3-2-4-6-8-11-30-12-10-13-33-35(30)27-52(44(33)57)36-18-19-38(54)49-42(36)55/h10,12-17,28-29,34,36-37,46,53H,2-9,11,18-27H2,1H3,(H,49,54,55)/t29-,34-,36?,37-/m1/s1
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| Chemical Name |
3-[7-[10-[[(2S)-2-(4-chlorophenyl)-3-[4-[(5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl]piperazin-1-yl]-3-oxopropyl]amino]decyl]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 115 mg/mL (144.04 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2525 mL | 6.2624 mL | 12.5249 mL | |
| 5 mM | 0.2505 mL | 1.2525 mL | 2.5050 mL | |
| 10 mM | 0.1252 mL | 0.6262 mL | 1.2525 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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