Cat. No.: HY-183480

Asulacrine

(Synonyms: CI-921; NSC 343499)

Asulacrine (CI-921) is an orally active DNA intercalating topoisomerase II inhibitor. Asulacrine binds to DNA via intercalation, with its acridine chromophore intercalated between base pairs and substituents located in the major/minor grooves, which stabilizes DNA against acid denaturation. Asulacrine acts as a cell cycle inhibitor, disruptor, and arrest inducer, slowing cell progression in late S/G2 phase, causing G2 phase arrest and inducing unbalanced growth. Asulacrine inhibits cell growth, clonogenicity, and colony formation, and leads to histological destruction of tumor cells. Compared to cells in exponential growth phase, Asulacrine exhibits lower toxicity to quiescent cells; its activity depends on cationic properties, and it has better water solubility and metabolic stability. Asulacrine can be used in research related to leukemia, lung cancer, colon cancer, breast cancer, melanoma, adriamycin-resistant mammary adenocarcinoma, and mouse solid tumors.

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

CAS No.: 80841-47-0
Formula: C₂₄H₂₄N₄O₄S
Molecular Weight:464.54

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

Asulacrine Chemical Structure

CAS No.: 80841-47-0

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Biological Activity
- Description
- IC₅₀ & Target
- In Vitro
- In Vivo
Chemical Information
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References
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Biological Activity

Description

IC₅₀ & Target^[2]

Topoisomerase II

All Topoisomerase Isoforms :

In Vitro

Asulacrine (CI-921) (80 nM, 190 nM; 1 h pulse incubation) reduces the colony formation rate of exponentially growing Chinese hamster ovary cells by 50%^[3].
Continuous incubation of exponentially growing Friend erythroleukemia cells with Asulacrine (9.5 nM) for 24 h inhibits cell growth by 50%^[3].
Asulacrine (67.5 nM; 1 h pulse incubation, followed by 23 h in drug-free medium) inhibits the growth of exponentially growing Friend erythroleukemia cells by 50% at 24 h post-exposure^[3].
Continuous incubation with Asulacrine (10-50 nM; 24 h) slows the proliferation rate of exponentially growing Friend erythroleukemia cells and prolongs their progression through late S phase and G₂ phase; in contrast, 50 nM of this agent induces irreversible G₂ phase arrest, complete growth arrest, and unbalanced growth accompanied by increased RNA and protein content^[3].
Asulacrine (10-100 nM; 1 h pulse incubation, followed by 23 h in drug-free medium) causes transient S-phase and G₂M-phase arrest in exponentially growing Friend erythroleukemia cells, while doses of 50 nM and 100 nM induce prolonged G₂M-phase arrest and polyploid cells. In addition, the 100 nM dose increases cellular RNA content^[3].
Asulacrine (25-100 nM; 1 h pulse incubation, followed by up to 23 h in drug-free medium) causes S-phase accumulation and prolongs S-phase progression in exponentially growing Chinese hamster ovary cells. Specifically, 100 nM induces persistent G₂M-phase arrest, and all tested concentrations increase the RNA content of G₂M-phase cells^[3].
Asulacrine (10-50 nM; 7 h continuous incubation with vinblastine) slows the progression of exponentially growing Friend erythroleukemia cells through late S and G₂ phases; a concentration of 50 nM causes severe S-phase arrest and complete mitotic block within 30 min, while both concentrations have no effect on G₁ phase exit^[3].
Asulacrine (10-50 nM; 7 h continuous incubation with vinblastine) stabilizes chromatin in exponentially growing Friend erythroleukemia cells, rendering it resistant to acid denaturation, which supports DNA intercalation as its binding mechanism^[3].

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

Cell Proliferation Assay^[3]

Cell Line:

exponentially growing Friend erythroleukemic (FL) cells
Concentration:

9.5 nM; 67.5 nM
Incubation Time:

24 h (continuous incubation); 1 h pulse followed by 24 h in drug-free medium
Result:

Inhibited FL cell growth by 50% relative to untreated control cultures after 24 h, with >90% of remaining cells viable.

Cell Cycle Analysis^[3]

Cell Line:

exponentially growing Friend erythroleukemic (FL) cells
Concentration:

1, 10, 50 nM
Incubation Time:

Continuous exposure; analyzed at 4, 8 and 24 h
Result:

Slowed S-phase progression and induced S/G2 accumulation at 10 nM.
Almost completely prevented cell division and caused marked G2/M accumulation at 50 nM.

Cell Cycle Analysis^[3]

Cell Line:

exponentially growing Friend erythroleukemic (FL) cells
Concentration:

10, 50, 100 nM
Incubation Time:

1 h (pulse incubation, followed by 23 h in drug-free medium)
Result:

Caused a small accumulation of cells in S and G₂M phases at 4 h, with cells subsequently dividing and returning to normal cell cycle distribution by 24 h.
Caused accumulation of cells in S phase at 4 h and near-total accumulation in G₂M phase at 8 h; by 24 h, some cells had divided to reenter G₁ and S phases, while others progressed to higher ploidy levels.
Caused a 72% increase in RNA content of G₂M cells measured 24 h post-exposure.

Cell Cycle Analysis^[3]

Cell Line:

exponentially growing Chinese hamster ovary (CHO) cells
Concentration:

25, 50, 100 nM
Incubation Time:

1 h (pulse incubation, followed by up to 23 h in drug-free medium)
Result:

Caused accumulation of cells in S phase at 4 h, with prolonged slowdown in S phase transit at 8 h.
By 24 h, cells treated with 25 nM or 50 nM had mostly divided and reentered the cell cycle, while 100 nM continued to block a large number of cells in G₂M phase.
All concentrations induced a small percentage of higher-ploidy cells, and 25 nM, 50 nM, and 100 nM caused increases in G₂M cell RNA content measured 24 h post-exposure.

In Vivo

Asulacrine (CI-921) exhibits potent in vivo antitumor activity against a variety of mouse solid tumors, human xenografts, and adriamycin-resistant mouse tumors. It shows synergistic activity when combined with Cisplatin (HY-17394) and has favorable oral bioavailability^[3].
Asulacrine (20 mg/kg/dose; intraperitoneal injection; administered on days 1, 5, and 9; total dose 60 mg/kg) exhibits the optimal antitumor activity among the tested administration regimens in F₁ hybrid mice intravenously inoculated with Lewis lung cancer cells, prolongs the lifespan of mice by 228%, and enables long-term survival on day 60 in 10 out of 11 mice^[5].
Asulacrine (30 mg/kg/dose; intraperitoneal or intravenous injection; administered on days 1, 5, and 9; total dose 90 mg/kg) exhibits moderate antitumor activity in F₁ hybrid mice subcutaneously inoculated with P388 leukemia cells, prolonging the maximum lifespan of mice by up to 48%, but no long-term surviving mice are observed^[5].
Asulacrine (30 mg/kg per dose; intraperitoneal injection; administered on days 1, 5 and 9; total dose 90 mg/kg) exhibits the optimal antileukemic activity among the tested administration regimens in F₁ hybrid mice intraperitoneally inoculated with P388 leukemia cells, prolongs the lifespan of mice by 210%, and enables long-term survival up to day 50 in 5 out of 6 mice^[5].
Asulacrine (3.9-45 mg/kg per dose; intraperitoneal injection; administered according to different regimens starting on day 9) prolongs the survival of mice with advanced Lewis lung cancer, and a significant linear correlation exists between the total administered dose and lifespan extension. Tumor responses are accompanied by histological tumor cell destruction; however, in subcutaneous tumor models, tumor volume does not decrease immediately even when obvious tumor cell killing occurs^[4].
Asulacrine (20 mg/kg per dose; intraperitoneal injection; administered on days 9, 12, and 15) induces histological destruction of pulmonary tumor nodules in mice with advanced Lewis lung cancer, characterized by tumor cell swelling, multinucleation, reduction in pulmonary tumor nodules, and disappearance of visible plaques on the lung surface^[4].
Asulacrine (30 mg/kg; i.p.; single administration) induces G2 phase arrest in subcutaneous Lewis lung cancer cells in mice. The proportion of G2 phase tumor cells increases significantly at 8 h post-administration and reaches maximal accumulation at 24 h^[4].

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

Animal Model:

F₁ hybrid mice (DBA/2J male × C57BL/6J female; mixed sex; body weight-matched in 1g intervals)^[5]
Dosage:

8.9 mg/kg (single i.p. day 1); 20 mg/kg (single i.p. day 1; daily i.p. days 1-5); 30 mg/kg (intermittent i.p. days 1,5,9); 35 mg/kg (daily i.p. days 1-9); 45 mg/kg (single i.p. day 1); 90 mg/kg total (intermittent i.p. days 1,5,9; intermittent i.v. days 1,5,9); 150 mg/kg total (intermittent p.o. days 1,5,9)
Administration:

i.p. (single dose day 1; intermittent days 1,5,9; daily days 1-5; daily days 1-9); i.v. (intermittent days 1,5,9); p.o. (intermittent days 1,5,9)
Result:

Achieved 5/6 mice surviving 50 days, a 210% increase in lifespan (ILS) at optimal total dose of 90 mg/kg via intermittent i.p. schedule (30 mg/kg per dose, days 1,5,9).
Achieved 2/6 mice surviving 50 days, a 102% ILS at optimal dose of 20 mg/kg via single i.p. dose schedule (day 1).
Showed no significant difference in ILS between 8.9 and 45 mg/kg via single i.p. dose schedule (day 1).
Achieved 1/6 mice surviving 50 days, a 169% ILS at optimal dose of 29.5 mg/kg via daily i.p. schedule (days 1-5).
Achieved 1/6 mice surviving 50 days, a 99% ILS at optimal dose of 35 mg/kg via daily i.p. schedule (days 1-9).
Achieved 1/6 mice surviving 50 days, a 136% ILS at optimal total dose of 90 mg/kg via intermittent i.v. schedule (days 1,5,9).
Produced no long-term survivors, a maximal 65% ILS at optimal total dose of 150 mg/kg via intermittent p.o. schedule (days 1,5,9).

Animal Model:

F₁ hybrid mice (DBA/2J male × C57BL/6J female; mixed sex; body weight-matched in 1g intervals)^[5]
Dosage:

13.3 mg/kg (intermittent i.p. days 1,5,9); 20 mg/kg (intermittent i.p. days 1,5,9; single i.p. day 1; intermittent i.v. days 5,9,13); 29.5 mg/kg (daily i.p. days 1-5); 30 mg/kg (intermittent i.p. days 1,5,9); 60 mg/kg total (intermittent i.p. days 1,5,9; intermittent i.v. days 5,9,13); 66 mg/kg (daily i.p. days 1-9); 150 mg/kg total (intermittent p.o. days 5,9,13)
Administration:

i.p. (intermittent days 1,5,9; single dose day 1; daily days 1-5; daily days 1-9); i.v. (intermittent days 5,9,13); p.o. (intermittent days 5,9,13)
Result:

Achieved 10/11 mice surviving 60 days, a 228% ILS at optimal total dose of 60 mg/kg via intermittent i.p. schedule (20 mg/kg per dose, days 1,5,9), with good activity across three dose levels (13.3, 20, 30 mg/kg per dose).
Achieved 1/6 mice surviving 60 days, a 61% ILS at optimal dose of 20 mg/kg via single i.p. dose schedule (day 1).
Achieved 3/11 mice surviving 60 days, a 68% ILS at optimal dose of 29.5 mg/kg via daily i.p. schedule (days 1-5).
Achieved 2/11 mice surviving 60 days, a 142% ILS at optimal dose of 66 mg/kg via daily i.p. schedule (days 1-9).
Achieved 9/12 mice surviving 60 days, a 134% ILS at optimal total dose of 60 mg/kg via intermittent i.v. schedule (days 5,9,13).
Produced no long-term survivors, a 132% ILS at optimal total dose of 150 mg/kg via intermittent p.o. schedule (days 5,9,13).

Animal Model:

F₁ hybrid mice (DBA/2J male × C57BL/6J female; mixed sex; body weight-matched in 1g intervals)^[5]
Dosage:

29.5 mg/kg (daily i.p. days 1-5); 30 mg/kg (intermittent i.p. days 1,5,9; intermittent i.v. days 1,5,9); 45 mg/kg (single i.p. day 1); 53 mg/kg (daily i.p. days 1-9); 90 mg/kg total (intermittent i.p. days 1,5,9; intermittent i.v. days 1,5,9)
Administration:

i.p. (single dose day 1; daily days 1-5; daily days 1-9; intermittent days 1,5,9); i.v. (intermittent days 1,5,9)
Result:

Achieved a maximal 48% ILS at optimal total dose of 90 mg/kg via intermittent i.p. schedule (30 mg/kg per dose, days 1,5,9), with activity across four dose levels, and was superior to single-dose or daily schedules.
Produced similar efficacy to the intermittent i.p. schedule via intermittent i.v. schedule (30 mg/kg per dose, days 1,5,9).
Achieved a 21% ILS at optimal dose of 45 mg/kg via single i.p. dose schedule (day 1), with activity across one to two dose levels.
Achieved a 29% ILS at optimal dose of 29.5 mg/kg via daily i.p. schedule (days 1-5), with activity across one to two dose levels.
Achieved a 36% ILS at optimal dose of 53 mg/kg via daily i.p. schedule (days 1-9), with activity across one to two dose levels.
Observed no long-term survivors in any treated group.

Animal Model:

B6D2F1 hybrid (i.v. inoculation with 10⁶ Lewis lung tumour cells)^[4]
Dosage:

3.9-45 mg/kg (various total doses up to 135 mg/kg)
Administration:

i.p.; various frequencies (daily, every 12 h, every 24 h, every 2 days, every 3 days, every 4 days, every 10 days); various durations (single dose, 3 doses, 5 doses, 6 doses, 9 doses, 15 doses, 3×12 h every 10 days ×3)
Result:

Resulted in 40-70% long-term survivors when treatment initiated on day 1 or 5 post-inoculation.
Achieved a median survival of 35 days with a tumour growth delay of 13 days when treatment initiated on day 9 post-inoculation.
Produced lifespan extension (ILS) ranging from 37% to 153%, with the highest ILS (153%) observed with 20 mg/kg every 4 days ×6 (total 120 mg/kg).
Demonstrated a highly significant linear correlation between total administered dose and lifespan extension (r=0.85, P<0.001 for optimal doses per schedule; r=0.79, P<0.001 for all doses).
Caused lung tumour nodules to show increased cross-sectional area with swollen, pale-staining, and multinucleate cells 3 days after the first 20 mg/kg dose on day 9.
Reduced tumour colony numbers, with tumours consisting of large foamy cells, giant cells, fibroblasts, and fibrous connective tissue 3 days after the second 20 mg/kg dose.
Resulted in lungs showing mostly normal tissue with rare, indistinct cell collections and occasional giant cells 5 days after the third 20 mg/kg dose.

Animal Model:

B6D2F1 hybrid (s.c. inoculation with 10⁶ Lewis lung tumour cells, tumours reached 0.5-1.0 cm in diameter at 8 days post-inoculation)^[4]
Dosage:

20 mg/kg; 30 mg/kg
Administration:

i.p.; q3d ×3 (20 mg/kg); single dose (30 mg/kg)
Result:

Caused swollen cells, multinucleate giant cells, and intercellular spaces throughout the tumour 3 days after the first 20 mg/kg dose.
Resulted in tumours showing swollen, pleomorphic, multinucleate cells with pyknotic/fragmented nuclei and increased eosinophilic cytoplasm 5 days after the third 20 mg/kg dose, with no significant reduction in tumour size despite extensive cell killing.
Induced a significant increase in G2-phase tumour cells by 8 h post-treatment, reaching a maximum at 24 h after a single 30 mg/kg dose.
Showed reduced G2 arrest with lower doses.

Chemical Information

CAS No. 80841-47-0
Molecular Weight 464.54
Formula C₂₄H₂₄N₄O₄S
SMILES

O=C(C1=CC=CC2=C1N=C3C(C=CC=C3C)=C2NC4=CC=C(NS(=O)(C)=O)C=C4OC)NC
Synonyms

CI-921; NSC 343499
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

Handling Instructions (2659 KB)

References

[1]. Hays SJ, Huang CC. Deuterium, tritium, and carbon-14 labeling of 9-[[2-methoxy-4-[(methylsulfonyl)amino]phenyl]amino]-N,5-dimethylacridinecarboxamide (CI-921), a new antitumor agent. J Labelled Comp Radiopharm. 1984;21(6):575-586.

[2]. Gellerman G. Recent Synthetic Approaches to Anti-cancer 9-Anilinoacridines. A Review. Org Prep Proced Int. 2012;44(3):187-221.

[3]. Traganos F, Bueti C, Darzynkiewicz Z, Melamed MR. Effects of a New Amsacrine Derivative, N-5-Dimethyl-9-(2-methoxy-4-methylsulfonylamino)phenylamino-4-acridinecarboxamide, on Cultured Mammalian Cells. Cancer Res. 1987;47(2):424-432.

[4]. Baguley BC, et al. Effects of CI-921, an analogue of amsacrine, on advanced Lewis lung tumours in mice: relevance to clinical trials. European journal of cancer & clinical oncology. 1988 Feb;24(2):211-8. [Content Brief]

[5]. Baguley BC, et al. Schedule dependence of activity of the amsacrine analogue CI-921 towards P388 leukaemia and Lewis lung carcinoma. European journal of cancer & clinical oncology. 1985 Nov;21(11):1337-41. [Content Brief]

[6]. Paxton JW, et al. The clinical pharmacokinetics of N-5-dimethyl-9-[(2-methoxy-4-methyl-sulfonylamino)phenylamino]-4 -acridinecarboxamide (CI-921) in a phase 1 trial. Cancer chemotherapy and pharmacology. 1988;22(3):235-40. [Content Brief]

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Asulacrine

All Topoisomerase Isoforms

Biological Activity

Chemical Information

Purity & Documentation

References

Calculators

Help & FAQs

Asulacrine Related Classifications

HY-183480 Related Classifications