Delving into the Latest Updates on Scyllitol with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

1,3,5/2,4,6-cyclohexanehexol, Cocositol, Quercinitol

+ [5]

Target

APP

Mechanism

APP inhibitors(Beta amyloid A4 protein inhibitors)

Therapeutic Areas

Nervous System Diseases

Active Indication

Alzheimer Disease

Inactive Indication

AggressionAgitationBipolar I disorder+ [1]

Originator Organization

Transition Therapeutics, Inc.

Active Organization

Transition Therapeutics, Inc.

Inactive Organization

OPKO Health, Inc.Transition Therapeutics Ireland Ltd.

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

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Structure

Molecular FormulaC6H12O6

InChIKeyCDAISMWEOUEBRE-CDRYSYESSA-N

CAS Registry488-59-5

ABSTRACTHere we present a “breathing” vessel consisting of expanded polytetrafluoroethylene, which allows gas exchange but no liquid permeation. The bacterial culture inside needs only agitation to promote air supply. Using this setup, a Bacillus subtilis cell factory for scyllo-inositol production grew to produce scyllo-inositol efficiently. The results indicate that our approach represents a sustainable “greener” approach for the cell factory.

24 Jul 2024·Applied and Environmental Microbiology

Efficient pathway-driven scyllo -inositol production from myo -inositol using thermophilic cells and mesophilic inositol dehydrogenases: a novel strategy for pathway control

Article

Author: Kurashiki, Ryota ; Ishikawa, Shu ; Yokoyama, Kyosuke ; Okumura, Yuta ; Suzuki, Hirokazu ; Makino, Kohei ; Fukui, Kaho ; Ono, Tatsuya ; Yoshida, Ken-ichi ; Ohshiro, Takashi ; Takahashi, Masahiro ; Endo, Hirofumi

ABSTRACT Mesophilic enzymes, which are active at moderate temperatures, may dominate enzymatic reactions even in the presence of thermophilic crude enzymes. This study was conducted to investigate this hypothesis with mesophilic inositol dehydrogenases (IolG and IolX) produced in Geobacillus kaustophilus HTA426. To ensure the efficient production of mesophilic enzymes, we first screened for promoters induced at moderate temperatures using transcriptome analysis and identified four genes highly expressed at 30°C in the thermophile. We further characterized these promoters using fluorescent reporter assays to determine that the mti3 promoter could direct efficient gene expression at 40°C. We cloned the promoter into an Escherichia coli–Geobacillus shuttle plasmid and confirmed that the resulting vector functioned in G. kaustophilus and other thermophiles. We then used this vector for the cooperative expression of the iolG and iolX genes from Bacillus subtilis 168. G. kaustophilus cells carrying the expression vector were incubated at 60°C for cellular propagation and then at 40°C for the production of IolG and IolX. When the cells were permeabilized, IolG and IolX acted as catalysts to convert exogenous myo -inositol into scyllo -inositol at 30°C. In a scaled-up reaction, 10 g of myo -inositol was converted to 1.8 g of scyllo -inositol, which was further purified to yield 970 mg of pure powder. Notably, myo -inositol was degraded by intrinsic enzymes of G. kaustophilus at 60°C but not at 30°C, supporting our initial hypothesis. We indicate that this approach is useful for preparing enzyme cocktails without the need for purification. IMPORTANCE Enzyme cocktails are commonly employed for cell-free chemical synthesis; however, their preparation involves cumbersome processes. This study affirms that mesophilic enzymes in thermophilic crude extracts can function as specific catalysts at moderate temperatures, akin to enzyme cocktails. The catalyst was prepared by permeabilizing cells without the need for concentration, extraction, or purification processes; hence, its preparation was considerably simpler compared with conventional methods for enzyme cocktails. This approach was employed to produce pure scyllo -inositol from an economical substrate. Notably, this marks the first large-scale preparation of pure scyllo -inositol, holding potential pharmaceutical significance as scyllo -inositol serves as a promising agent for certain diseases but is currently expensive. Moreover, this approach holds promise for application in pathway engineering within living cells. The envisioned pathway is designed without chromosomal modification and is simply regulated by switching culture temperatures. Consequently, this study introduces a novel platform for both whole-cell and cell-free synthetic systems.

01 Jun 2024·Current Opinion in Biotechnology

Microbial synthesis of health-promoting inositols

Review

Author: Bott, Michael ; Yoshida, Ken-Ichi

D-chiro-inositol and scyllo-inositol are known for their health-promoting properties and promising as ingredients for functional foods. Strains of Bacillus subtilis and Corynebacterium glutamicum were created by metabolic engineering capable of inexpensive production of these two rare inositols from myo-inositol, which is the most common inositol in nature. In addition, further modifications have enabled the synthesis of the two rare inositols from the much-cheaper carbon sources, glucose or sucrose.

100 Deals associated with Scyllitol

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Scyllitol	-	DB03106

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Alzheimer Disease	Phase 3	-	Transition Therapeutics, Inc.	-
Bipolar I disorder	Discovery	FR	OPKO Health, Inc.	01 Aug 2012
Bipolar I disorder	Discovery	PL	OPKO Health, Inc.	01 Aug 2012
Bipolar I disorder	Discovery	CA	OPKO Health, Inc.	01 Aug 2012
Bipolar I disorder	Discovery	CZ	OPKO Health, Inc.	01 Aug 2012
Bipolar I disorder	Discovery	ES	OPKO Health, Inc.	01 Aug 2012
Alzheimer Disease	Discovery	GB	Transition Therapeutics Ireland Ltd.	-
Alzheimer Disease	Discovery	US	Transition Therapeutics Ireland Ltd.	-
Alzheimer Disease	Discovery	ES	Transition Therapeutics Ireland Ltd.	-
Alzheimer Disease	Discovery	CA	Transition Therapeutics Ireland Ltd.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01735630 (CTgov)	Phase 2	Alzheimer Disease \| Aggression \| Agitation	350	ELND005 (ELND005)	yluwizyudy(jzsoomzpib) = aazqdfrvcz kcnvgqyskl (zboffcwqqy, jykpgxmxlt - wlajuvtxbv) View more	-	15 Aug 2016
				Placebo (Placebo)	yluwizyudy(jzsoomzpib) = salcmuienb kcnvgqyskl (zboffcwqqy, jxrzndfcuy - adtmyfdenl) View more
NCT01766336 (CTgov)	Phase 2	Alzheimer Disease \| Aggression \| Agitation	296	ELND005 (ELND005/ELND005)	cdmzstkabu(wldcvghbgw) = saqssklmvp etyfyvfgto (tjumdfeotu, qfsfwqjipv - ajfgnkngvs) View more	-	13 May 2016
				Placebo+ELND005 (Placebo/ELND005)	cdmzstkabu(wldcvghbgw) = shbywevqzx etyfyvfgto (tjumdfeotu, andmqggawt - jwcrarrbkm) View more
NCT01791725 (DS201, CTgov)	Phase 2	Down Syndrome	23	ELND005 (ELND005 BID)	bjsxmtipdt(srijsrikjd) = loofsctwqe scancqrrxu (pkrrfvqzmy, rjladcnumk - cgsguhgwct) View more	-	29 Jan 2016
				ELND005 (ELND005 QD)	bjsxmtipdt(srijsrikjd) = skuanumxyo scancqrrxu (pkrrfvqzmy, kqrxryqikw - yickltjylb) View more
NCT00934050 (CTgov)	Phase 2	Alzheimer Disease	103	Placebo+ELND005 (Placebo/ELND005 250mg BID)	(ncikmyaoix) = jedsvdglyf sarzdrnoiu (ybxuajawbc, oeeffqckue - yoicktohue) View more	-	13 May 2015
				ELND005 (250 mg/ELND005 250 mg BID)	(ncikmyaoix) = auzwozvjrx sarzdrnoiu (ybxuajawbc, hvitsxmmyo - rxxttmzfkp) View more
AD201 (AAIC2012)	Not Applicable	Alzheimer Disease	351	ELND005 (Scyllo-inositol) 250mg	fzuvtdmjde(thrgjoqrti) = ihtgfzrdgb ybmixxojwj (adbkzlrrut, -36% - -45%)	-	01 Jul 2012
				ELND005 (Scyllo-inositol) 1000mg	fzuvtdmjde(thrgjoqrti) = essizsyzdx ybmixxojwj (adbkzlrrut, -61% - -64%)
NCT00568776 (CTgov)	Phase 2	Alzheimer Disease	353	Placebo (Placebo BID)	jfpmcnoxdh(yefcuiymmg) = qwigcnajiz klsufcyvys (rqpwxchuoo, nstlgjvfzp - ozhuwfncsj) View more	-	29 Mar 2012
				ELND005 (ELND005 250 mg BID)	jfpmcnoxdh(yefcuiymmg) = kmbtcjwfph klsufcyvys (rqpwxchuoo, tebgysbauj - hvkwdqneiv) View more
AAIC2011	Not Applicable	Alzheimer Disease	353	ELND005 250mg	zhvunlhspw(mojzswucxp) = gxfgfzcpow ekkqochomw (ufxusqevbw )	-	01 Jul 2011
AAIC2009	Not Applicable	Plaque, Amyloid	-	ELND005 (scylloinositol)	kiuyjtxafr(cfatdjmhpl) = phcnfuijfz rasnfllkaz (mblrduealn )	-	01 Jul 2009