MA203 (PROTAC 41) at a concentration of 5 µM reduced CHK1 levels in MIA PaCa-2 pancreatic ductal adenocarcinoma (PDAC) cells by approximately 50% and exhibited a strong affinity for CHK1 (binding rate of 97% at a concentration of 1.0 µM) [1]. MA203 (2 µM, 24 h) significantly reduced CHK1 levels in Hydroxyurea (HU)-treated MIA PaCa-2 and MOLT-4 cells by up to 80% and 50%, respectively [1]. The CHK1 degradation mediated by MA203 (2 μM, 3–24 h) was a time-dependent process accompanied by changes in phosphorylation status in MIA PaCa-2 cells, indicating that this degradation enhanced DNA damage signaling [1]. MA203 combined with HU significantly reduced the expression level of CHK1 in MOLT-4, MOLM-13, RS4-11 and HCT116 cells to 50%-40% of that in untreated cells, and attenuated CHK1 expression in MOLM-13 cells [1]. In MIA PaCa-2 cells, the dose-dependent attenuation of CHK1 expression by MA203 (1-5 µM, 24 h) combined with 5 µM Irinotecan was better than that by using it alone [1]. In MOLT-4 cells, the half-maximum CHK1 degradation concentration (DC50 = 387.4 nM) reached by MA203 (0.5-10 µM, 24 h) combined with 2 µM Cytarabine was significantly lower than that of the single use (DC50 = 3.86 µM) [1]. MA203 (0.5–10 μM, 24 h) enhances HU-induced DNA replication stress, leading to DNA double-strand breaks and replication catastrophe in MIA PaCa-2 and MOLT-4 cells [1]. MA203 (2 μM, 24–48 h) + HU significantly increases the proportion of early and late apoptotic cells in MIA PaCa-2 and MOLT-4 cells [1]. MA203 (2 μM, 24 h) promotes dendritic cell survival, either alone or in combination with HU [1]. MA203 (2 μM, 24 h) significantly enhances Ara-C-mediated cell death, as evidenced by a 62% reduction in the Ara-C concentration (IC50) required to kill 50% of cells in MOLT-4 cells [1]. After 24 hours of treatment with MA203 (2 µM, 24 h) + HU, the expression of multiple key proteins in MIA PaCa-2 cells was significantly reduced. These proteins regulate tumorigenesis and DNA damage repair, including transcription factor 7 (TCF7), cell cycle-associated protein 7 (CDCA7), origin recognition complex subunit 1 (ORC1), and Werner syndrome RecQ-like helicase (WRN), while RRM2 levels were slightly increased [1]. Treatment with MA203 (2 µM, 24–48 h) + HU resulted in more significant G1/S phase arrest; induced a higher apoptosis rate, accompanied by upregulation of BAX/BIM and downregulation of BCL-XL/XIAP; more significant loss of mitochondrial membrane potential and stronger caspase activation [1].

MA203 (PROTAC 41) (12 μM, 48 hours) significantly inhibited the proliferation of human cells in zebrafish larvae and had no obvious toxicity to zebrafish larvae at effective doses [1].

Western Blot Analysis[1]
Cell Types: MIA PaCa-2 cells, MOLT-4 cells
Tested Concentrations: 2 µM
Incubation Duration: 24 h
Experimental Results: Specifically degraded CHK1, and this degradation is enhanced by HU-induced CHK1 activation. Did not affect other checkpoint kinases or common CRBN substrates.

---

Western Blot Analysis[1]
Cell Types: MIA PaCa-2 cells
Tested Concentrations: 2 µM
Incubation Duration: 3 h, 6 h, 10 h, 16 h, 24 h
Experimental Results: Illustrated that the degradation of CHK1 started already after 3 h in MIA PaCa-2 cells, to yield a 50%-70% reduction of CHK1 after 10-16 h. Suppressed the HU-induced hyperphosphorylation of CHK1 at S296 but augmented its HU-induced hyperphosphorylation at S345. Did not alter CHK2 levels over different time points.

---

Western Blot Analysis[1]
Cell Types: MIA PaCa-2, MOLT-4
Tested Concentrations: 0.5 μM, 1 μM, 2 μM, 5 μM, 10μM
Incubation Duration: 24 h
Experimental Results: Significantly increased γH2AX levels (4.2-fold). Achieved a Dmax of 92% at a DC50 of 1.51 µM in MIA PaCa-2 cells, and a Dmax of 93.2% at a DC50 of 5.35 µM in MOLT-4 cells. Significant 15.7-fold induction of ATM phosphorylation at S1981.

---

Apoptosis Analysis[1]
Cell Types: MIA PaCa-2 cells, HCT116 cells, MOLT-4 cells, MOLM-13 cells
Tested Concentrations: 2 μM
Incubation Duration: 24 h, 48 h
Experimental Results: After 48 h, the percentages of early and late apoptotic cells significantly increased to 15% and 14% in MIA PaCa-2 cell cultures; A significant rise in the early apoptotic cell population to 33% was observed. In HCT116 cells, caused early and late apoptosis were significantly increased when combined with 0.5 mM HU for 48 h. An accumulation of late apoptotic cells (30%) occurred upon treatment. Significantly augmented cell populations in early apoptosis to 19% and in late apoptosis to 15% after 24 h in MOLT-4 cells. In the presence of 1 mM HU, triggered early (48%) and late (24%) apoptotic cell death. In MOLM-13 cells, triggered a significant accumulation of early apoptotic cells (33%), enhanced late apoptosis of MOLM-13 cells to 50%. Normal human cells did not exhibit any significant impairment in viability upon treatment.

[1]. Identification of a Proteolysis-Targeting-Chimera that Addresses Activated Checkpoint Kinase-1 Reveals its Non-Catalytic Functions in Tumor Cells. Angew Chem Int Ed Engl. 2025 Oct 17:e202514788.

C38H45N9O8

755.82

Typically exists as solids at room temperature

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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 Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

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
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

 (Please use freshly prepared in vivo formulations for optimal results.)