NPASS Compound

Natural Product: NPC476550

Natural Product ID	NPC476550
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	1-Butanesulfinothioic acid, S-butyl ester
IUPAC Name	1-butylsulfinylsulfanylbutane
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	10420162
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0001161] Thiosulfinic acid esters

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 29 28 0 0 0 0 0 0 0 0999 V2000 -4.2625 1.1078 0.1231 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7483 -0.1479 0.7429 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4130 -0.5681 0.1520 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9102 -1.8419 0.7949 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3460 -2.2943 0.0599 S 0 0 0 0 0 0 0 0 0 0 0 0 1.2478 -1.0504 0.3938 S 0 0 0 0 0 0 0 0 0 0 0 0 1.5834 -0.7386 1.8339 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3356 0.3303 -0.6947 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4651 1.2665 -0.5147 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8363 0.7415 -0.6912 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2376 -0.3625 0.2423 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4802 1.7736 -0.2595 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0102 0.9003 -0.6825 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8226 1.6700 0.9065 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5109 -0.9440 0.6025 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5929 -0.0192 1.8216 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6813 0.2456 0.3307 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5875 -0.6996 -0.9447 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6986 -2.6007 0.6444 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8155 -1.6159 1.8844 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3896 0.9431 -0.5885 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2547 -0.0672 -1.7431 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3959 1.7866 0.4886 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2906 2.1219 -1.2362 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0641 0.4423 -1.7456 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5650 1.5871 -0.4985 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7156 -1.3073 0.0104 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1588 -0.0578 1.3154 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3396 -0.6013 0.1316 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 1 12 1 0 1 13 1 0 1 14 1 0 2 15 1 0 2 16 1 0 3 17 1 0 3 18 1 0 4 19 1 0 4 20 1 0 8 21 1 0 8 22 1 0 9 23 1 0 9 24 1 0 10 25 1 0 10 26 1 0 11 27 1 0 11 28 1 0 11 29 1 0 M END

Standard InCHIKey	XSHPYKKTJQSNFE-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C8H18OS2/c1-3-5-7-10-11(9)8-6-4-2/h3-8H2,1-2H3
SMILES	CCCCSS(=O)CCCC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	194.08	Volume:	192.733 ? Van der Waals volume.
Dense:	1.007	LogP:	2.814 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.102 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.753 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	0.0
TPSA:	23.06 ? Topological Polar Surface Area.	H-Bond Acceptor:	1.0
H-Bond Donor:	0.0	Rings:	0.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.353	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.339	Fsp³:	1.0
MCE-18:	1.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.014	Fluc inhibitor:	0.279 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.006 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.835	Promiscuous compounds:	0.88

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.635	MDCK Permeability:	-4.593
Pgp-inhibitor:	0.808	Pgp-substrate:	0.0
PAMPA:	0.12 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.413
20% Bioavailability (F20%):	0.024	30% Bioavailability (F30%):	0.397
50% Bioavailability (F50%):	0.188

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.725	MRP1:	0.743
Plasma Protein Binding (PPB):	72.479%	Volume Distribution (VD):	0.183
Fu:	28.225% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.994
OATP1B3 inhibitor:	0.992	BCRP inhibitor:	0.003
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.985	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.999	CYP2C19-substrate:	0.018
CYP2C9-inhibitor:	0.991	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.926	CYP2D6-substrate:	0.002
CYP3A4-inhibitor:	0.816	CYP3A4-substrate:	0.984
CYP2B6-substrate:	1.0	CYP2C8-inhibitor:	0.675
HLM stability:	0.999 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

9.672

Half-life (T1/2):

0.668

ADMET: Toxicity

hERG Blockers:	0.085	hERG Blockers (10um):	0.232
Human Hepatotoxicity (H-HT):	0.041	Drug-induced Liver Injury (DILI):	0.923
AMES Toxicity:	0.591	Rat Oral Acute Toxicity:	0.713
Maximum Recommended Daily Dose:	0.811	Skin Sensitization:	1.0
Carcinogencity:	0.345	Eye Corrosion:	0.999
Eye Irritation:	1.0	Respiratory Toxicity:	0.998
Drug-induced Neurotoxicity:	0.001	Ototoxicity:	0.002
Hematotoxicity:	0.002	Drug-induced Nephrotoxicity:	0.01
Genotoxicity:	0.453	RPMI-8226 Immunitoxicity:	0.014
A549 Cytotoxicity:	0.0	Hek293 Cytotoxicity:	0.224
BCF:	1.979 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	3.835 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.077 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.592 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO8374	Allium siculum	Species	Amaryllidaceae	Eukaryota	bulb	n.a.	n.a.	PMID[12141853]
NPO8374	Allium siculum	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8374	Allium siculum	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IZ	21

Activity Type	# Activity
Organism	21

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2710	Organism	Streptococcus agalactiae	Streptococcus agalactiae	IZ	=	0	mm	PMID[12141853]
NPT2710	Organism	Streptococcus agalactiae	Streptococcus agalactiae	IZ	=	30	mm	PMID[12141853]
NPT2710	Organism	Streptococcus agalactiae	Streptococcus agalactiae	IZ	=	34	mm	PMID[12141853]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IZ	=	10	mm	PMID[12141853]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IZ	=	34	mm	PMID[12141853]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IZ	=	38	mm	PMID[12141853]
NPT19	Organism	Escherichia coli	Escherichia coli	IZ	=	0	mm	PMID[12141853]
NPT19	Organism	Escherichia coli	Escherichia coli	IZ	=	10	mm	PMID[12141853]
NPT19	Organism	Escherichia coli	Escherichia coli	IZ	=	16	mm	PMID[12141853]
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	IZ	=	0	mm	PMID[12141853]
NPT1521	Organism	Stenotrophomonas maltophilia	Stenotrophomonas maltophilia	IZ	=	0	mm	PMID[12141853]
NPT1521	Organism	Stenotrophomonas maltophilia	Stenotrophomonas maltophilia	IZ	=	8	mm	PMID[12141853]
NPT1521	Organism	Stenotrophomonas maltophilia	Stenotrophomonas maltophilia	IZ	=	16	mm	PMID[12141853]
NPT2923	Organism	Klebsiella pneumoniae subsp. pneumoniae	Klebsiella pneumoniae subsp. pneumoniae	IZ	=	0	mm	PMID[12141853]
NPT2923	Organism	Klebsiella pneumoniae subsp. pneumoniae	Klebsiella pneumoniae subsp. pneumoniae	IZ	=	8	mm	PMID[12141853]
NPT314	Organism	Bacillus cereus	Bacillus cereus	IZ	=	8	mm	PMID[12141853]
NPT314	Organism	Bacillus cereus	Bacillus cereus	IZ	=	34	mm	PMID[12141853]
NPT314	Organism	Bacillus cereus	Bacillus cereus	IZ	=	40	mm	PMID[12141853]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC476550 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	26373
0.1-0.2	21938
0.2-0.3	1331
0.3-0.4	132
0.4-0.5	38
0.5-0.6	23
0.6-0.7	12
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8696	High Similarity	NPC286695
0.8333	Intermediate Similarity	NPC603612
0.76	Intermediate Similarity	NPC80396
0.76	Intermediate Similarity	NPC154642
0.75	Intermediate Similarity	NPC12904
0.7308	Intermediate Similarity	NPC149299
0.72	Intermediate Similarity	NPC154396
0.6957	Remote Similarity	NPC166804
0.6923	Remote Similarity	NPC80641
0.68	Remote Similarity	NPC223249
0.6667	Remote Similarity	NPC223677
0.6364	Remote Similarity	NPC99700
0.625	Remote Similarity	NPC326758
0.619	Remote Similarity	NPC327450
0.619	Remote Similarity	NPC234005
0.6154	Remote Similarity	NPC322892
0.6087	Remote Similarity	NPC3693
0.6087	Remote Similarity	NPC476549
0.6	Remote Similarity	NPC163345
0.5833	Remote Similarity	NPC140229
0.5769	Remote Similarity	NPC250028
0.5769	Remote Similarity	NPC236579
0.5769	Remote Similarity	NPC80234
0.5769	Remote Similarity	NPC203531
0.5769	Remote Similarity	NPC256163
0.5769	Remote Similarity	NPC40597
0.5769	Remote Similarity	NPC178643
0.56	Remote Similarity	NPC53541
0.56	Remote Similarity	NPC248233
0.5484	Remote Similarity	NPC71761
0.5417	Remote Similarity	NPC143211
0.5417	Remote Similarity	NPC476548
0.5385	Remote Similarity	NPC40965
0.5185	Remote Similarity	NPC81263
0.5185	Remote Similarity	NPC86545
0.5185	Remote Similarity	NPC286498
0.5185	Remote Similarity	NPC223374
0.5185	Remote Similarity	NPC196442
0.5185	Remote Similarity	NPC301398
0.5185	Remote Similarity	NPC608162
0.5185	Remote Similarity	NPC609004
0.5172	Remote Similarity	NPC600941

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC476550 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6761
0.1-0.2	2232
0.2-0.3	129
0.3-0.4	19
0.4-0.5	5
0.5-0.6	2
0.6-0.7	0
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8182	Intermediate Similarity	NPD900	Pre-clinical
0.5294	Remote Similarity	NPD631	Phase 4
0.5143	Remote Similarity	NPD630	Approved

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data