NPASS Compound

Natural Product: NPC173019

Natural Product ID	NPC173019
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Alpha-Terthienylmethanol
IUPAC Name	[5-(5-thiophen-2-ylthiophen-2-yl)thiophen-2-yl]methanol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL90170
PubChem CID	454740
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002021] Bi- and oligothiophenes

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 27 29 0 0 0 0 0 0 0 0999 V2000 6.0907 -0.0609 1.3871 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6965 0.1117 0.0624 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2968 -0.2353 -0.0547 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5741 -1.3464 -0.3148 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2337 -1.2932 -0.3473 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6121 -0.1326 -0.1206 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9030 0.9831 0.1591 S 0 0 0 0 0 0 0 0 0 0 0 0 0.2192 0.2445 -0.0859 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3521 1.5028 0.1636 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6734 1.5732 0.1354 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4158 0.4730 -0.1234 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1488 -0.7589 -0.3445 S 0 0 0 0 0 0 0 0 0 0 0 0 -3.8370 0.2741 -0.2122 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5959 -0.8022 -0.4666 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9201 -0.7152 -0.4913 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5072 0.5377 -0.2432 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0567 1.5931 0.0293 S 0 0 0 0 0 0 0 0 0 0 0 0 6.9867 -0.4698 1.4233 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2757 -0.5018 -0.6529 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9201 1.1777 -0.2081 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1495 -2.3070 -0.5004 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6261 -2.2190 -0.5642 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3421 2.3652 0.3701 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2046 2.5441 0.3249 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0642 -1.7870 -0.6593 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5876 -1.6041 -0.7027 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5629 0.8535 -0.2103 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 6 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 11 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 7 3 1 0 12 8 1 0 17 13 1 0 1 18 1 0 2 19 1 0 2 20 1 0 4 21 1 0 5 22 1 0 9 23 1 0 10 24 1 0 14 25 1 0 15 26 1 0 16 27 1 0 M END

Standard InCHIKey	WAYZWWNNJZMQCQ-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C13H10OS3/c14-8-9-3-4-12(16-9)13-6-5-11(17-13)10-2-1-7-15-10/h1-7,14H,8H2
SMILES	OCc1ccc(s1)c1ccc(s1)c1cccs1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	277.99	Volume:	256.233 ? Van der Waals volume.
Dense:	1.085	LogP:	3.445 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.903 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.911 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	15.0
TPSA:	20.23 ? Topological Polar Surface Area.	H-Bond Acceptor:	1.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.736	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.476	Fsp³:	0.077
MCE-18:	14.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.484	Fluc inhibitor:	0.997 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.926 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.423 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.647	Promiscuous compounds:	0.115

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.752	MDCK Permeability:	-4.727
Pgp-inhibitor:	0.11	Pgp-substrate:	0.009
PAMPA:	0.038 ? 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):	0.039
20% Bioavailability (F20%):	0.698	30% Bioavailability (F30%):	0.795
50% Bioavailability (F50%):	0.867

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.45	MRP1:	0.411
Plasma Protein Binding (PPB):	95.346%	Volume Distribution (VD):	0.399
Fu:	3.62% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.265
OATP1B3 inhibitor:	0.812	BCRP inhibitor:	0.012
BSEP inhibitor:	0.945

ADMET: Metabolism

CYP1A2-inhibitor:	0.415	CYP1A2-substrate:	0.784
CYP2C19-inhibitor:	0.01	CYP2C19-substrate:	0.891
CYP2C9-inhibitor:	0.992	CYP2C9-substrate:	0.078
CYP2D6-inhibitor:	0.999	CYP2D6-substrate:	0.511
CYP3A4-inhibitor:	0.785	CYP3A4-substrate:	0.998
CYP2B6-substrate:	0.756	CYP2C8-inhibitor:	0.989
HLM stability:	0.009 ? 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):

5.994

Half-life (T1/2):

0.464

ADMET: Toxicity

hERG Blockers:	0.262	hERG Blockers (10um):	0.403
Human Hepatotoxicity (H-HT):	0.811	Drug-induced Liver Injury (DILI):	0.998
AMES Toxicity:	0.87	Rat Oral Acute Toxicity:	0.229
Maximum Recommended Daily Dose:	0.035	Skin Sensitization:	0.447
Carcinogencity:	0.951	Eye Corrosion:	0.032
Eye Irritation:	0.79	Respiratory Toxicity:	0.735
Drug-induced Neurotoxicity:	0.271	Ototoxicity:	0.664
Hematotoxicity:	0.215	Drug-induced Nephrotoxicity:	0.571
Genotoxicity:	0.998	RPMI-8226 Immunitoxicity:	0.084
A549 Cytotoxicity:	0.019	Hek293 Cytotoxicity:	0.39
BCF:	1.635 ? 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:	4.295 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.75 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.302 ? 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
NPO21382	Eutypa lata	Species	Diatrypaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12608846]
NPO2842	Garcinia lucida	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17880175]
NPO33375	eclipata prostrata	Species	n.a.	n.a.	aerial parts	n.a.	n.a.	PMID[25443644]
NPO33375	eclipata prostrata	Species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21382	Eutypa lata	Species	Diatrypaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26309	Ahnfeltiopsis flabelliformis	Species	Phyllophoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21251	Tabernaemontana odoratissima	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19837	Euonymus latifolius	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19410	Clutia abyssinica	Species	Peraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20431	Centaurea canariensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19272	Alcyonium fauri	Species	Alcyoniidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20295	Eclipta prostrata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20295	Eclipta prostrata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21507	Ephedra intermedia	Species	Ephedraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO20295	Eclipta prostrata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21507	Ephedra intermedia	Species	Ephedraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21507	Ephedra intermedia	Species	Ephedraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO20295	Eclipta prostrata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO21507	Ephedra intermedia	Species	Ephedraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO20295	Eclipta prostrata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO3468	Astragalus floccosifolius	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20101	Eria acutifolia	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17908	Rhododendron reticulatum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26309	Ahnfeltiopsis flabelliformis	Species	Phyllophoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19559	Cetraria pseudocomplicata	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20295	Eclipta prostrata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14172	Rhopaloeides odorabile	Species	Spongiidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18749	Corydalis vernyi	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11034	Mnium pseudopunctatum	Species	Mniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19410	Clutia abyssinica	Species	Peraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21507	Ephedra intermedia	Species	Ephedraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20648	Streptomyces cellulosae	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO21382	Eutypa lata	Species	Diatrypaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20982	Morus lactea	Species	Sulidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20233	Marchantia paleacea	Species	Marchantiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21251	Tabernaemontana odoratissima	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19837	Euonymus latifolius	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2842	Garcinia lucida	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17115	Kielmeyera petiolaris	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20431	Centaurea canariensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19272	Alcyonium fauri	Species	Alcyoniidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20718	Hypericum elegans	Species	Hypericaceae	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
IC50	2

Activity Type	# Activity
Individual protein	1
Others	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1592	Individual protein	Dipeptidyl peptidase IV	Homo sapiens	IC50	=	3350.0	nM	PMID[25443644]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2	Others	Unspecified	n.a.	IC50	=	4000.0	nM	PMID[9873605]

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 NPC173019 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	43218
0.1-0.2	6497
0.2-0.3	111
0.3-0.4	19
0.4-0.5	5
0.5-0.6	6
0.6-0.7	1
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.6216	Remote Similarity	NPC24122
0.5667	Remote Similarity	NPC195713
0.561	Remote Similarity	NPC472171
0.5263	Remote Similarity	NPC602622
0.5227	Remote Similarity	NPC472172
0.5122	Remote Similarity	NPC8981
0.5111	Remote Similarity	NPC219963

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC173019 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7110
0.1-0.2	1987
0.2-0.3	48
0.3-0.4	5
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

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