Delving into the Latest Updates on 9-Aminocamptothecin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

9-Amino-20-S-camptothecin, Aminocamptothecin, NSC-629971 (racemic--isomer)

+ [5]

Target

TOP1

Mechanism

TOP1 inhibitors(DNA topoisomerase I inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesDigestive System Disorders+ [5]

Active Indication-

Inactive Indication

Advanced Lung Non-Small Cell CarcinomaAdvanced Renal Cell CarcinomaCutaneous T-Cell Lymphoma+ [8]

Originator Organization

Arisyn Therapeutics Inc

Active Organization-

Inactive Organization

National Cancer Institute

Biogen, Inc.Arisyn Therapeutics Inc

+ [1]

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Structure

Molecular FormulaC20H17N3O4

InChIKeyFUXVKZWTXQUGMW-FQEVSTJZSA-N

CAS Registry91421-43-1

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.
PURPOSE: Phase II trial to study the effectiveness of aminocamptothecin in treating patients with recurrent or unresectable epithelial ovarian cancer that has been previously treated with platinum-based chemotherapy.

Start Date01 Dec 1995

Sponsor / Collaborator

NYU Langone Health

[+2]

100 Clinical Results associated with 9-Aminocamptothecin

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100 Translational Medicine associated with 9-Aminocamptothecin

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100 Patents (Medical) associated with 9-Aminocamptothecin

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293

Literatures (Medical) associated with 9-Aminocamptothecin

01 Sep 2024·International Journal of Biological Macromolecules

Development of a RNA-protein complex based smart drug delivery system for 9-hydroxycamptothecin

Article

Author: Shen, Xiao ; Wang, Yan ; Wang, Pingping ; Yan, Xing ; Li, Zhenhua ; Yang, Yi ; Zhang, Tong ; Zhou, Zhihua ; Xiong, Ying ; Tian, Ernuo

Camptothecin (CPT) is a monoterpenoid indole alkaloid with a wide spectrum of anticancer activity. However, its application is hindered by poor solubility, lack of targeting specificity, and severe side effects. Structural derivatization of CPT and the development of suitable drug delivery systems are potential strategies for addressing these issues. In this study, we discovered that the protein Cytochrome P450 Family 1 Subfamily A Member 1 (CYP1A1) from Homo sapiens catalyzes CPT to yield 9-hydroxycamptothecin (9-HCPT), which exhibits increased water solubility and cytotoxicity. We then created a RNA-protein complex based drug delivery system with enzyme and pH responsiveness and improved the targeting and stability of the nanomedicine through protein module assembly. The subcellular localization of nanoparticles can be visualized using fluorescent RNA probes. Our results not only identified the protein CYP1A1 responsible for the structural derivatization of CPT to synthesize 9-HCPT but also offered potential strategies for enhancing the utilization of silk-based drug delivery systems in tumor therapy.

01 Oct 2023·Bioorganic Chemistry

Improved anti-tumor activity of fluorinated camptothecin derivatives 9-fluorocamptothecin and 7-ethyl-9-fluorocamptothecin on hepatocellular carcinoma by targeting topoisomerase I

Article

Author: Bai, Yin-Peng ; Zhang, Zhi-Jun ; Zhu, Li-Zu ; Zhang, Mi ; Yan, Jia-Xuan ; Liu, Ying-Qian ; Xu, Chuan-Rui ; Wang, Zhi-Ping ; Peng, Li-Zeng ; Yang, Cheng-Jie ; Luo, Hong-Bo ; Li, Lei

Primary liver cancer is one of the most common malignant cancers of the digestive system that lacks effective chemotherapeutic drugs in clinical settings. Camptothecin (CPT) and its derivatives have been approved for cancer treatment; however, their application is limited by their systemic toxicity. For lead optimization in new drug discovery stages, fluorination is an effective and robust approach to increase the bioavailability and optimize the pharmacokinetics of candidate compounds, thereby improving their efficacy. To obtain new and highly active CPT derivatives, we designed, synthesized, and evaluated two new fluorinated CPT derivatives, 9-fluorocamptothecin (A1) and 7-ethyl-9-fluorocamptothecin (A2), in this study. In vitro, A1 and A2 exhibited more robust anti-tumor activity than topotecan (TPT) in various cancer cells, particularly hepatocellular carcinoma (HCC) cells. In vivo, A1 and A2 exhibited greater anti-tumor activity than TPT in both AKT/Met induced primary HCC mouse models and implanted HepG2 cell xenografts. Acute toxicity tests revealed that A1 and A2 were not lethal and did not cause significant body weight loss at high doses. Moreover, A1 and A2 exhibited no significant toxicity in the mouse liver, heart, lung, spleen, kidney, and hematopoietic systems at therapeutic doses. Mechanistically, A1 and A2 blocked HCC cell proliferation by inhibiting the enzymatic activity of Topo I, subsequently inducing DNA damage, cell cycle arrest, and apoptosis. In summary, our results indicate that fluorination improves the anti-tumor activity of CPT while decreasing its toxicity and highlight the application potential of fluorination products A1 and A2 in clinical settings.

01 Mar 2022·American Journal of Physiology-Cell PhysiologyQ3 · BIOLOGY

Chloride channels with ClC-1-like properties differentially regulate the excitability of dopamine receptor D1- and D2-expressing striatal medium spiny neurons

Q3 · BIOLOGY

Article

Author: Nass, Sara R. ; Yarotskyy, Viktor ; Hahn, Yun K. ; Knapp, Pamela E. ; Lark, Arianna R. S. ; Hauser, Kurt F. ; McQuiston, A. Rory ; Marone, Michael G.

Dynamic chloride (Cl−) regulation is critical for synaptic inhibition. In mature neurons, Cl− influx and extrusion are primarily controlled by ligand-gated anion channels (GABAA and glycine receptors) and the potassium chloride cotransporter K+-Cl− cotransporter 2 (KCC2), respectively. Here, we report for the first time, to our knowledge, a presence of a new source of Cl− influx in striatal neurons with properties similar to chloride voltage-gated channel 1 (ClC-1). Using whole cell patch-clamp recordings, we detected an outwardly rectifying voltage-dependent current that was impermeable to the large anion methanesulfonate (MsO−). The anionic current was sensitive to the ClC-1 inhibitor 9-anthracenecarboxylic acid (9-AC) and the nonspecific blocker phloretin. The mean fractions of anionic current inhibition by MsO−, 9-AC, and phloretin were not significantly different, indicating that anionic current was caused by active ClC-1-like channels. In addition, we found that Cl− current was not sensitive to the transmembrane protein 16A (TMEM16A; Ano1) inhibitor Ani9 and that the outward Cl− rectification was preserved even at a very high intracellular Ca2+ concentration (2 mM), indicating that TMEM16B ( Ano2) did not contribute to the total current. Western blotting and immunohistochemical analyses confirmed the presence of ClC-1 channels in the striatum mainly localized to the somata of striatal neurons. Finally, we found that 9-AC decreased action potential firing frequencies and increased excitability in medium spiny neurons (MSNs) expressing dopamine type 1 (D1) and type 2 (D2) receptors in the brain slices, respectively. We conclude that ClC-1-like channels are preferentially located at the somata of MSNs, are functional, and can modulate neuronal excitability.

100 Deals associated with 9-Aminocamptothecin

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External Link

KEGG	Wiki	ATC	Drug Bank
-	9-Aminocamptothecin	-	DB12515

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Esophageal Carcinoma	Phase 3	US	National Cancer Institute	01 Mar 1998
Stomach Cancer	Phase 3	US	National Cancer Institute	01 Mar 1998
Advanced Lung Non-Small Cell Carcinoma	Phase 3	US	National Cancer Institute	01 Jan 1998
Recurrent Hodgkin Lymphoma	Phase 3	US	National Cancer Institute	01 Apr 1996
Recurrent ovarian cancer	Phase 3	US	National Cancer Institute	01 Dec 1995
Cutaneous T-Cell Lymphoma	Phase 3	US	National Cancer Institute	01 May 1995
Neoplasms	Phase 3	-	Pfizer Inc.	-
Neoplasms	Phase 3	-	Biogen, Inc.	-
Neoplasms	Phase 3	-	National Cancer Institute	-
Neoplasms	Phase 3	-	Arisyn Therapeutics Inc	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00002745 (CALGB 9551, Pubmed \| Cancer Chemother Pharmacol)	Phase 2	Lymphoma	37	9-aminocamptothecin dimethylacetamide	(fruyfmrqad) = fbynknssbi ibtcccxoxo (wdakoiqzzi ) View more	-	01 Apr 2009
	Phase 2	Lymphoma	37	9-aminocamptothecin/colloidal dispersion	(fruyfmrqad) = ssieioorop ibtcccxoxo (wdakoiqzzi ) View more	-	01 Apr 2009
NCT00002671 (Pubmed \| J Urol)	Phase 2	Ovarian Cancer Second line	60	9-aminocamptothecin	(qwatrkzdnb) = bwobmdvtsk bzxcxpamix (davheymvpx ) View more	Positive	01 Jan 2004