NPASS Compound

Natural Product: NPC160850

Natural Product ID	NPC160850
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	DRUQKRWRXOUEGS-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	12315236
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000296] Benzodioxoles

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 32 35 0 0 0 0 0 0 0 0999 V2000 1.2269 -1.2602 -0.3636 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5631 -1.5482 -0.5172 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5467 -0.6264 -0.1494 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1695 0.5875 0.3743 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8181 0.8824 0.5311 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8717 -0.0482 0.1587 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5370 0.3201 0.3458 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5342 -0.5238 -0.3757 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2260 -1.5383 0.4954 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9666 -0.7420 1.3481 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5940 0.1571 0.5062 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6675 0.4577 -0.6315 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0167 1.7841 -0.4673 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7173 1.6292 -0.0876 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7868 -0.3232 -0.0089 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3361 1.3010 0.6494 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4051 0.6691 -0.0716 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9248 -0.6554 -0.1939 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4700 -2.0016 -0.6588 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8802 -2.4944 -0.9260 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5709 1.8500 0.9474 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7954 0.2934 1.4245 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1938 -1.0243 -1.2757 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9402 -2.0889 -0.1531 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5247 -2.2072 1.0232 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7679 1.0891 1.1105 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1278 0.3101 -1.6271 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5746 2.3446 0.3279 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1205 2.3627 -1.4131 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5357 0.2858 0.2665 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4969 1.0784 -1.0966 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3465 0.7206 0.5080 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 11 15 1 0 4 16 1 0 16 17 1 0 17 18 1 0 6 1 1 0 14 7 1 0 18 3 1 0 12 8 1 0 1 19 1 0 2 20 1 0 5 21 1 0 7 22 1 0 8 23 1 0 9 24 1 0 9 25 1 0 11 26 1 0 12 27 1 0 13 28 1 0 13 29 1 0 15 30 1 0 17 31 1 0 17 32 1 0 M END

Standard InCHIKey	DRUQKRWRXOUEGS-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C13H14O5/c14-13-9-5-15-12(8(9)4-16-13)7-1-2-10-11(3-7)18-6-17-10/h1-3,8-9,12-14H,4-6H2
SMILES	c1cc2c(cc1C1C3COC(C3CO1)O)OCO2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	250.08	Volume:	235.22 ? Van der Waals volume.
Dense:	1.063	LogP:	0.583 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.947 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.43 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	19.0
TPSA:	57.15 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.808	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.884	Fsp³:	0.538
MCE-18:	70.3 ? 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:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.042	Fluc inhibitor:	0.009 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.052 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.053 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.227	Promiscuous compounds:	0.157

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.68	MDCK Permeability:	-4.677
Pgp-inhibitor:	0.124	Pgp-substrate:	0.039
PAMPA:	0.581 ? 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):	0.002
20% Bioavailability (F20%):	0.032	30% Bioavailability (F30%):	0.001
50% Bioavailability (F50%):	0.409

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.976	MRP1:	0.773
Plasma Protein Binding (PPB):	88.034%	Volume Distribution (VD):	0.22
Fu:	12.884% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.352
OATP1B3 inhibitor:	0.737	BCRP inhibitor:	0.029
BSEP inhibitor:	0.994

ADMET: Metabolism

CYP1A2-inhibitor:	0.399	CYP1A2-substrate:	0.707
CYP2C19-inhibitor:	0.927	CYP2C19-substrate:	0.082
CYP2C9-inhibitor:	0.987	CYP2C9-substrate:	0.958
CYP2D6-inhibitor:	0.989	CYP2D6-substrate:	0.983
CYP3A4-inhibitor:	0.021	CYP3A4-substrate:	0.101
CYP2B6-substrate:	0.582	CYP2C8-inhibitor:	0.001
HLM stability:	0.296 ? 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):

4.687

Half-life (T1/2):

1.624

ADMET: Toxicity

hERG Blockers:	0.145	hERG Blockers (10um):	0.478
Human Hepatotoxicity (H-HT):	0.552	Drug-induced Liver Injury (DILI):	0.814
AMES Toxicity:	0.769	Rat Oral Acute Toxicity:	0.449
Maximum Recommended Daily Dose:	0.428	Skin Sensitization:	0.497
Carcinogencity:	0.661	Eye Corrosion:	0.061
Eye Irritation:	0.905	Respiratory Toxicity:	0.654
Drug-induced Neurotoxicity:	0.619	Ototoxicity:	0.442
Hematotoxicity:	0.316	Drug-induced Nephrotoxicity:	0.201
Genotoxicity:	0.695	RPMI-8226 Immunitoxicity:	0.081
A549 Cytotoxicity:	0.095	Hek293 Cytotoxicity:	0.255
BCF:	0.85 ? 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:	3.252 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.322 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.062 ? 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
NPO24778	Sesamum orientale	Species	Pedaliaceae	Eukaryota	n.a.	seed	n.a.	PMID[11540412]
NPO24778	Sesamum orientale	Species	Pedaliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24778	Sesamum orientale	Species	Pedaliaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO24778	Sesamum orientale	Species	Pedaliaceae	Eukaryota	Leaf	n.a.	n.a.	Database[FooDB]
NPO24778	Sesamum orientale	Species	Pedaliaceae	Eukaryota	Seed	n.a.	n.a.	Database[FooDB]
NPO24778	Sesamum orientale	Species	Pedaliaceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO24778	Sesamum orientale	Species	Pedaliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO24778	Sesamum orientale	Species	Pedaliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24778	Sesamum orientale	Species	Pedaliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO24778	Sesamum orientale	Species	Pedaliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO24778	Sesamum orientale	Species	Pedaliaceae	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

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

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 NPC160850 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	23293
0.1-0.2	24935
0.2-0.3	1280
0.3-0.4	247
0.4-0.5	65
0.5-0.6	22
0.6-0.7	8
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
0.7174	Intermediate Similarity	NPC171928
0.7174	Intermediate Similarity	NPC158526
0.7174	Intermediate Similarity	NPC129687
0.7174	Intermediate Similarity	NPC33611
0.7174	Intermediate Similarity	NPC16830
0.7174	Intermediate Similarity	NPC100223
0.6792	Remote Similarity	NPC469981
0.66	Remote Similarity	NPC227160
0.66	Remote Similarity	NPC82111
0.6346	Remote Similarity	NPC189474
0.6111	Remote Similarity	NPC14022
0.6111	Remote Similarity	NPC601703
0.6071	Remote Similarity	NPC298317
0.6071	Remote Similarity	NPC255566
0.5862	Remote Similarity	NPC88640
0.5862	Remote Similarity	NPC101153
0.5862	Remote Similarity	NPC193666
0.5862	Remote Similarity	NPC123526
0.5862	Remote Similarity	NPC608725
0.5593	Remote Similarity	NPC47181
0.5517	Remote Similarity	NPC101807
0.5424	Remote Similarity	NPC483653
0.54	Remote Similarity	NPC271208
0.54	Remote Similarity	NPC233224
0.54	Remote Similarity	NPC610263
0.5357	Remote Similarity	NPC171550
0.5357	Remote Similarity	NPC134764
0.5283	Remote Similarity	NPC137487
0.5273	Remote Similarity	NPC487685
0.5238	Remote Similarity	NPC311057
0.5238	Remote Similarity	NPC600032
0.52	Remote Similarity	NPC121783
0.52	Remote Similarity	NPC34902
0.52	Remote Similarity	NPC18449
0.5167	Remote Similarity	NPC474139
0.5094	Remote Similarity	NPC480478

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC160850 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4414
0.1-0.2	4632
0.2-0.3	97
0.3-0.4	7
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