Delving into the Latest Updates on Tasisulam Sodium with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Tasisulam, Tasisulam sodium (USAN), 他斯索兰

+ [6]

Target-

Action

stimulants

Mechanism

Apoptosis stimulants

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal DiseasesDigestive System Disorders+ [6]

Active Indication-

Inactive Indication

Acute Myeloid LeukemiaAdvanced cancerAdvanced Malignant Solid Neoplasm+ [14]

Originator Organization

Eli Lilly & Co.

Active Organization-

Inactive Organization

Eli Lilly & Co.

License Organization-

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

RegulationOrphan Drug (United States)

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Structure/Sequence

Molecular FormulaC11H6BrCl2NO3S2

InChIKeyWWONFUQGBVOKOF-UHFFFAOYSA-N

CAS Registry519055-62-0

View All Structures (2)

The purpose of this study is to evaluate whether tasisulam acts as an inducer of CYP3A using midazolam as a sensitive and specific probe substrate of CYP3A.
The study will also assess the safety and tolerability of tasisulam and midazolam given in combination and document any antitumor activity with tasisulam.

Start Date01 Sep 2010

Sponsor / Collaborator

Eli Lilly & Co.

NCT01185548

/ TerminatedPhase 1

The Effect of Tasisulam on the CYP2C9-Mediated Metabolism of Tolbutamide: A Pharmacokinetic Interaction Study in Cancer Patients With Advanced and/or Metastatic Solid Tumors or Lymphoma

The purpose of this study was to assess the effect of tasisulam as an inhibitor of CYP2C9, using tolbutamide as a probe substrate. This study was to have 3 treatment periods, and continued access in an extension period. Period 1 is 4 days in length. Periods 2 and 3 are each approximately 28 days in length. Due to the early termination of the trial, only 1 Period 3 participant enrolled in the extension period before study termination.

Start Date01 Jul 2010

Sponsor / Collaborator

Eli Lilly & Co.

EUCTR2009-014591-21-AT

/ Not yet recruitingNot Applicable

A Randomized Phase 3 Study of Tasisulam Administered as an Intravenous Infusion on Day 1 of a 28-Day Cycle vs. Paclitaxel as Second-Line Treatment in Patients with Metastatic Melanoma

Start Date24 Mar 2010

Sponsor / Collaborator

Eli Lilly & Co.

100 Clinical Results associated with Tasisulam Sodium

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100 Translational Medicine associated with Tasisulam Sodium

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100 Patents (Medical) associated with Tasisulam Sodium

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44

Literatures (Medical) associated with Tasisulam Sodium

01 Jun 2025·Biochemical Pharmacology

Targeting RBM39 with Tasisulam enhances TRAIL-induced apoptosis through DR5 upregulation and Bcl-2 downregulation in renal cell carcinoma

Article

Author: Kim, Hunmin ; Shin, Yerim ; Jun, Heejin ; Yeo, Mirae ; Jang, Ji Hoon ; Park, Cho-Young ; Kim, Haein ; Kim, Joo-Young ; Kim, Eunhee ; Kang, Sebyung ; Lee, Tae-Jin

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in tumor cells but faces limitations due to resistance mechanisms involving anti-apoptotic regulators such as Bcl-2. This study investigates Tasisulam, a molecular glue degrader, that degrades RNA-binding motif protein 39 (RBM39), as a sensitizer for TRAIL-mediated apoptosis in renal cell carcinoma (RCC). Tasisulam enhances TRAIL-induced apoptosis by activating both extrinsic and intrinsic apoptotic pathways, achieved through upregulation of death receptor 5 (DR5) and downregulation of B-cell lymphoma 2 (Bcl-2). Importantly, Tasisulam selectively sensitizes RCC cells to TRAIL-induced apoptosis without affecting normal cells.RBM39 knockdown mimicked the effects of Tasisulam by upregulating DR5, downregulating Bcl-2, and enhancing TRAIL-induced apoptosis, suggesting RBM39 as a critical regulator of these pathways. To address TRAIL instability in vivo, AaLS/TRAIL nanoparticles were employed in combination with Tasisulam in a Caki-1 xenograft model. This combination significantly reduced tumor volume and weight compared to single treatments, without observed toxicity. These findings demonstrate that Tasisulam sensitizes RCC cells to TRAIL-induced apoptosis through RBM39-dependent DR5 upregulation and Bcl-2 downregulation. This combination strategy holds significant promise as a potential solution to overcoming TRAIL resistance and advancing more effective treatment outcomes for RCC.

01 Dec 2024·Genes & Genomics

Recent advances in anticancer mechanisms of molecular glue degraders: focus on RBM39-dgrading synthetic sulfonamide such as indisulam, E7820, tasisulam, and chloroquinoxaline sulfonamide

Review

Author: Kim, Joo-Young ; Jang, Ji Hoon ; Lee, Tae-Jin

Synthetic sulfonamide anticancer drugs, including E7820, indisulam, tasisulam, and chloroquinoxaline sulfonamide, exhibit diverse mechanisms of action and therapeutic potential, functioning as molecular glue degraders. E7820 targets RBM39, affecting RNA splicing and angiogenesis by suppressing integrin α2. Phase I studies have demonstrated some stability in advanced solid malignancies; however, further efficacy studies are required. Indisulam causes G1 cell cycle arrest and delays the G1/S transition by modulating splicing through RBM39 degradation via DCAF15. Despite its limited initial efficacy, it shows promise in combination therapies, particularly for hematopoietic malignancies and gliomas. Tasisulam inhibits VEGF signaling, suppresses angiogenesis, and induces apoptosis. Although early trials indicated broad activity, safety concerns have halted its development. Chloroquinoxaline sulfonamide, initially investigated for cell cycle arrest and topoisomerase II inhibition, was discontinued owing to its limited efficacy and toxicity, despite promising initial results. Recent studies revealed the structural interaction of E7820 with DCAF15 and RBM39, although phase II trials on myeloid malignancies have shown limited efficacy. Indisulam is effective against glioblastoma and neuroblastoma, with potential synergy in combination therapies and metabolic disruption. Recent research on tasisulam reveals its potential in cancer therapy by targeting RBM39 degradation through DCAF15-mediated pathways. Understanding these mechanisms could lead to new treatments that affect alternative splicing and improve cancer therapies Overall, although these drugs exhibit promising mechanisms of action, further research is required to optimize their clinical efficacy and safety.

01 Oct 2024·Journal of Biological Chemistry

Deubiquitinating enzyme USP39 promotes the growth and metastasis of gastric cancer cells by modulating the degradation of RNA-binding protein RBM39

Article

Author: Li, Jia-Bin ; Wu, Shenglong ; Lu, Chengpiao ; Xu, Guoqiang ; Cai, Yunxin ; Ma, Jingjing ; Wang, Yuhong

It has been revealed recently that the RNA-binding motif protein RBM39 is highly expressed in several cancers, which results in poor patient survival. However, how RBM39 is regulated in gastric cancer cells is unknown. Here, affinity purification-mass spectrometry and a biochemical screening are employed to identify the RBM39-interacting proteins and the deubiquitinating enzymes that regulate the RBM39 protein level. Integration of the data obtained from these two approaches uncovers USP39 as the potential deubiquitinating enzyme that regulates RBM39 stability. Bioinformatic analysis discloses that USP39 is increased in gastric cancer tissues and its elevation shortens the duration of overall survival for gastric cancer patients. Biochemical experiments verify that USP39 and RBM39 interact with each other and highly colocalize in the nucleus. Expression of USP39 elevates while USP39 knockdown attenuates the RBM39 protein level and their interaction regulates this modulation and their colocalization. Mechanistic studies reveal that USP39 reduces the K48-linked polyubiquitin chains on RBM39, thus enhancing its stability and increasing the protein level by preventing its proteasomal degradation. USP39 overexpression promotes while its knockdown attenuates the growth, colony formation, migration, and invasion of gastric cancer cells. Interestingly, overexpression of RBM39 partially restores the impact of USP39 depletion, while RBM39 knockdown partially abolishes the effect of USP39 overexpression on the growth, colony formation, migration, and invasion of gastric cancer cells. Collectively, this work identifies the first DUB for RBM39 and elucidates the regulatory functions and the underlying mechanism, providing a possible alternative approach to suppressing RBM39 by inhibiting USP39 in cancer therapy.

100 Deals associated with Tasisulam Sodium

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External Link

KEGG	Wiki	ATC	Drug Bank
D09389	-	-	DB11941

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic melanoma	Phase 3	Spain	Eli Lilly & Co.	01 Dec 2009
Metastatic melanoma	Phase 3	Sweden	Eli Lilly & Co.	01 Dec 2009
Metastatic melanoma	Phase 3	South Korea	Eli Lilly & Co.	01 Dec 2009
Metastatic melanoma	Phase 3	United States	Eli Lilly & Co.	01 Dec 2009
Metastatic melanoma	Phase 3	Germany	Eli Lilly & Co.	01 Dec 2009
Metastatic melanoma	Phase 3	United Kingdom	Eli Lilly & Co.	01 Dec 2009
Metastatic melanoma	Phase 3	France	Eli Lilly & Co.	01 Dec 2009
Metastatic melanoma	Phase 3	Taiwan Province	Eli Lilly & Co.	01 Dec 2009
Metastatic melanoma	Phase 3	Israel	Eli Lilly & Co.	01 Dec 2009
Metastatic melanoma	Phase 3	Austria	Eli Lilly & Co.	01 Dec 2009

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01209832 (CTgov)	Phase 1	Advanced cancer \| Lymphoma	11	Midazolam (Midazolam)	rxkfadtbgs(zcynxjdeyo) = gzyjbabivq hbstnvyrbl (mwhjopvyyy, ibtoncakvp - hruqzdjwej) View more	-	18 Mar 2019
				Tasisulam+Midazolam (Midazolam + Tasisulam)	rxkfadtbgs(zcynxjdeyo) = ghejjdluuu hbstnvyrbl (mwhjopvyyy, uiogbrvqfw - toydvscsdr) View more
NCT00363766 (CTgov)	Phase 2	metastatic non-small cell lung cancer	52	LY573636 (LY573636 Target Cmax 420 µg/mL)	(pznkzguewk) = czkhmzedfv mpkgbnlfib (topbtzhwzz, twjmbiznov - yjdcpkdiur) View more	-	19 Oct 2018
				LY573636 (LY573636 Target Cmax 380 µg/mL)	(pznkzguewk) = hzajwgffmt mpkgbnlfib (topbtzhwzz, ahwycmmniy - awkpmfganv) View more
NCT01185548 (JZAR, CTgov)	Phase 1	Metastatic Solid Tumor \| Advanced cancer \| Lymphoma	4	Tasisulam+Tolbutamide	hcnqbdozua(nugujbdqcr) = ukzjhwnxpk cnieebrawm (ztwaqhyhgn, pvteqklinc - pwhitsnrxq) View more	-	19 Oct 2018
NCT01258348 (CTgov)	Phase 1	Metastatic Renal Cell Carcinoma	21	LY+Sunitinib (LY 340 μg/mL + Sunitinib 50 mg)	srbsuubncq(bskxqctaww) = oxuickztpi wrtzeighyc (rzelrfwpdb, bfmkkjopby - bcruilzuqw) View more	-	16 Oct 2018
				LY+Sunitinib (LY 300 μg/mL + Sunitinib 50/37.5 mg)	srbsuubncq(bskxqctaww) = runoexuxaa wrtzeighyc (rzelrfwpdb, jdtcovimjs - pfcpuecfyn) View more
NCT01214668 (CTgov)	Phase 1	Advanced Malignant Solid Neoplasm	31	LY+Dox (LY 300 μg/mL + Dox)	(iphsieffvy) = pldaqnmvhk hlfkaqkhez (dkuycderjz, hmvaffqkmm - wfwmktqjdz) View more	-	16 Oct 2018
				LY+Dox (LY 320 μg/mL + Dox)	(iphsieffvy) = fujfkjbjzx hlfkaqkhez (dkuycderjz, fsgwapnphc - jjevmnugfc) View more
NCT00718159 (CTgov)	Phase 1	Acute Myeloid Leukemia \| Thrombocythemia, Essential	23	LY573636-sodium	vmjcwejlwd(fahtqwpjdd) = ezvwdlbcik ptvhelmhul (iugvtjufbr, jaoyyzjyky - aqhlgmjchr) View more	-	16 Oct 2018
NCT00992225 (CTgov)	Phase 2	Metastatic breast cancer	43	LY573636-sodium	ninhftzhoc(rpaxsvnfgv) = dssoqlitwr hnmbhuerti (vkyxvxgtmj, xmfqzqcxen - yxvbyiqiud) View more	-	17 Jul 2018
NCT01006252 (SUMMIT-1, CTgov)	Phase 3	Metastatic melanoma	336	Tasisulam-sodium (Tasisulam-sodium)	(laclomoqia) = vvbtqxcgig nggwpkcunb (bmhismfcyl, intjvlbdfk - rseulqdaoh) View more	-	17 Jul 2018
				Paclitaxel (Paclitaxel)	(laclomoqia) = pfxrfkigxj nggwpkcunb (bmhismfcyl, qljegwlube - fhsyszipio) View more
NCT00383292 (CTgov)	Phase 2	Metastatic melanoma \| Unresectable Melanoma	130	tasisulam	yvdeqorvhf(nnuzmknhnn) = frfbvdnvjw rqgbygiyhy (dnfpwzebrt, yvfufispsj - zkcmrpymkj) View more	-	06 Jun 2018
NCT00490451 (CTgov)	Phase 2	Metastatic Soft Tissue Sarcoma	101	LY573636 (LY573636 Target Cmax 420 µg/mL)	(shppbnuxbw) = adccqfemxv vtynxukxiq (siszjxtfsz, qkwjzalcvy - rfsdqnyakm) View more	-	02 May 2018
				LY573636 (LY573636 Target Cmax 360 µg/mL)	(shppbnuxbw) = atuqtgwzrt vtynxukxiq (siszjxtfsz, gzzcfxljsk - zstpcpgjkg) View more