Cat. No.: HY-12388

N-Desmethyl clomipramine

Name: N-Desmethyl clomipramine
Brand: MedChemExpress
SKU: HY-12388
Availability: PreOrder

(Synonyms: Desmethylclomipramine; Norclomipramine)

N-Desmethyl clomipramine (Desmethylclomipramine; Norclomipramine) is the orally active major active metabolite of the tricyclic antidepressant Clomipramine (HY-B0457A), possessing multiple activities including anti-inflammatory, antioxidant, antibacterial, and antiparasitic effects. N-Desmethyl clomipramine blocks autophagosome-lysosome fusion, leading to the accumulation of LC3-II, p62, ATG7, WIPI2, and ATG5-12, reactivates the p53/p21 pathway, induces apoptosis through C-PARP and C-CAS3, and inhibits the proliferation, migration, and invasion of renal cancer cells. N-Desmethyl clomipramine inhibits LdTOPIA, inducing R-loop accumulation in the nucleus of Leishmania, ultimately causing parasite death. N-Desmethyl clomipramine can be used for research on depression, metastatic renal cell carcinoma, and leishmaniasis.

For research use only. We do not sell to patients.

CAS No.: 303-48-0
Formula: C₁₈H₂₁ClN₂
Molecular Weight:300.83

Storage:

Please store the product under the recommended conditions in the Certificate of Analysis.

Data Sheet (285 KB)

N-Desmethyl clomipramine Chemical Structure

CAS No.: 303-48-0

Size

Price

Stock

Quantity

Amount: USD 0.00

* Please select Quantity before adding items.

Top Publications Citing

Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- In Vitro
- In Vivo
Chemical Information
Purity & Documentation
References
Calculators
Help & FAQs
Classifications
Bioz

Biological Activity

Description

IC₅₀ & Target

^[3]^[4]^[5]

Caspase 3

PARP-1

TNF-α

Leishmania

All PAK Isoforms :

All Caspase Isoforms :

All PARP Isoforms :

All TNF Receptor Isoforms :

All Parasite Isoforms :

In Vitro

Bacterial InfectionAutophagyAnti-cancerApoptosisCell Cycle RegulationInnate ImmunityCytokines & ChemokinesParasitic Infection

Bacterial Infection

N-Desmethyl clomipramine (Norclomipramine) completely inhibits Mycobacterium tuberculosis topoisomerase-I activity in the DNA relaxation assay^[2].

Autophagy

N-Desmethyl clomipramine effectively blocks autophagic flux in KJ29 and Caki-2 ccRCC cells, leading to the accumulation of the autophagy markers p62 and LC3I/II; it also prevents autophagosome-lysosome fusion, resulting in the accumulation of ATG7, WIPI2, and ATG5-12 in KJ29 and Caki-2 ccRCC cells^[3].

Anti-cancer

Apoptosis

N-Desmethyl clomipramine (1-10 µM; 0-120 h) inhibits the proliferation of KJ29 and Caki-2 ccRCC cells in a dose-dependent manner, reduces migration, and enhances the growth-inhibitory effect of Sunitinib (HY-10255A); it also promotes apoptosis in KJ29 and Caki-2 ccRCC cells and enhances Sunitinib-induced apoptosis through activation of C-PARP and C-CAS3^[3].

Anti-cancer

Autophagy

Cell Cycle Regulation

N-Desmethyl clomipramine (5 µM) inhibits autophagy and reactivates the p53/p21 pathway in KJ29 and Caki-2 ccRCC cells^[3].

Innate Immunity

Cytokines & Chemokines

N-Desmethyl clomipramine (Desmethylclomipramine) (0.01-1 μM; 48 h) reduces TNFα secretion and nitrite levels in a dose-dependent manner in mouse primary cortical neuron-BV2 microglia co-cultures, but does not improve neuronal viability^[4].
N-Desmethyl clomipramine (1 μM; 16 h) upregulates Nfe2l2 gene expression in BV2 microglia under both inflammatory and non-inflammatory conditions, but does not regulate the expression of the Nrf2 target genes Gclm, Hmox1, or Nqo1^[4].

Parasitic Infection

N-Desmethyl clomipramine (10-40 μM) inhibits the DNA relaxation activity of LdTOPIA^[5].
N-Desmethyl clomipramine (2-100 μM; 72 h) exhibits potent antileishmanial activity against Leishmania donovani promastigotes and amastigotes, and is effective against clinically isolated antimony-resistant Leishmania isolates BHU575 and BHU814; its cytotoxicity to macrophages (Raw264.7 and THP1) is lower than its antileishmanial activity^[5].
N-Desmethyl clomipramine (10 μM; 0-48 h) treatment induces R-loop formation in Leishmania donovani DD8 parasites, as detected by the DRIB assay^[5].

Parasitic Infection

Innate Immunity

N-Desmethyl clomipramine (10 μM; 6-48 h) effectively clears Leishmania donovani DD8 amastigotes within RAW264.7 macrophages^[5].
N-Desmethyl clomipramine (10 μM; 48 h) reduces the intracellular amastigote burden of Leishmania donovani DD8, BHU575, and BHU814 in RAW264.7 macrophages^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Proliferation Assay^[3]

Cell Line:

KJ29 and Caki-2 ccRCC cell lines
Concentration:

1, 5, 10 µM (DCMI alone)
5 µM (DCMI in combination with 5 µM Sunitinib)
Incubation Time:

24 h
Result:

Resulted in a significant, dose-dependent reduction in cell proliferation.
The combined application (5 µM) with Sunitinib (5 µM) induced a dramatic inhibition of cell growth compared with each compound alone.

Cell Migration Assay ^[3]

Cell Line:

KJ29 and Caki-2 ccRCC cells
Concentration:

5 µM (DCMI alone or in combination with 5 µM Sunitinib)
Incubation Time:

0, 48, 120 h
Result:

Reduced cell migration after 48 h and 120 h compared with untreated cells.
The long-term combined treatment (120 h) with Sunitinib nearly completely arrested cell migration, leaving the wound area almost completely open.

Apoptosis Analysis^[3]

Cell Line:

KJ29 and Caki-2 ccRCC cells
Concentration:

5 µM (DCMI alone or in combination with 5 µM Sunitinib)
Incubation Time:

48 h
Result:

Enhanced the number of apoptotic nuclei compared with untreated cells.
The combined treatment with Sunitinib caused a greater number of apoptotic nuclei than either drug alone.

Western Blot Analysis^[3]

Cell Line:

KJ29 and Caki-2 ccRCC cells
Concentration:

5 µM (DCMI alone or in combination with 5 µM Sunitinib)
Incubation Time:

48 h
Result:

Showed higher C-PARP activation in both ccRCC cells.
The triggering of C-CAS3 was enhanced in Caki-2 cells.
The combined treatment with Sunitinib caused a stronger activation of both C-PARP and C-CAS3 than either drug alone.

Real Time qPCR^[4]

Cell Line:

BV2 microglia
Concentration:

1 μM
Incubation Time:

16 h
Result:

Upregulated Nfe2l2 gene expression under both inflammatory and non-inflammatory conditions but does not regulate the expression of the Nrf2 target genes Gclm, Hmox1 or Nqo1.

Immunofluorescence^[5]

Cell Line:

Leishmania donovani DD8 wild-type parasites
Concentration:

10 μM
Incubation Time:

0, 12, 24, 48 h
Result:

Induced increasing amounts of R-loops generated inside the nucleus with increasing time.

In Vivo

N-Desmethyl clomipramine (Desmethylclomipramine) (0.05-0.4 mg/kg; intravenous injection; infusion for 10 min; 30 min before PET measurement) occupied NET in non-human primates in a dose- and plasma concentration-dependent manner, with mean K_d values of 0.11 mg/kg and 4.4 ng/mL^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

Female cynomolgus monkeys (2.8-3.2 kg and 3.6-4.4 kg)^[1]
Dosage:

0.05, 0.2, 0.4 mg/kg
Administration:

i.v.; infused over 10 min; 30 min before PET measurements
Result:

Decreased BPND values in a dose-dependent manner.
Occupied NET with a mean estimated Kd of 0.11 mg/kg (0.15 mg/kg in the thalamus, 0.11 mg/kg in the brainstem, and 0.07 mg/kg in the anterior cingulate cortex).
Occupied NET with a mean estimated Kd of 4.4 ng/mL (5.7 ng/mL in the thalamus, 4.3 ng/mL in the brainstem, and 3.2 ng/mL in the anterior cingulate cortex).

Related Protocols :

Chemical Information

CAS No. 303-48-0
Molecular Weight 300.83
Formula C₁₈H₂₁ClN₂
SMILES

CNCCCN1C2=CC(Cl)=CC=C2CCC3=CC=CC=C31
Synonyms

Desmethylclomipramine; Norclomipramine
Structure Classification
- Others
Initial Source
- Endogenous metabolite
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (285 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Takano A, et al. NET occupancy by clomipramine and its active metabolite, desmethylclomipramine, in non-human primates in vivo. Psychopharmacology. 2011 Jul;216(2):279-86.

[2]. Temesszentandrási-Ambrus C, et al. Characterization of new, efficient Mycobacterium tuberculosis topoisomerase-I inhibitors and their interaction with human ABC multidrug transporters. PloS one. 2018;13(9):e0202749.

[3]. Patergnani S, et al. Autophagy inhibition potentiates anti-cancer activity of Sunitinib in kidney cancer cells. Biology direct. 2025 Jul 15;20(1):82.

[4]. Lipponen A, et al. In Vitro and In Vivo Pipeline for Validation of Disease-Modifying Effects of Systems Biology-Derived Network Treatments for Traumatic Brain Injury-Lessons Learned. International journal of molecular sciences. 2019 Oct 29;20(21):5395.

[5]. Das P, et al. Resolving the polycistronic aftermath: Essential role of topoisomerase IA in preventing R-loops in Leishmania. The Journal of biological chemistry. 2024 Apr;300(4):107162.

Calculators

Molarity Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Dilution Calculator

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Product Name:
Cat. No.:
Quantity:
MCE Japan Authorized Agent:

Product Name:
CAS No.:
Species:
Purity:
Quantity:

N-Desmethyl clomipramine

All PAK Isoforms

All Caspase Isoforms

All PARP Isoforms

All TNF Receptor Isoforms

All Parasite Isoforms