NPASS Compound

Natural Product: NPC31981

Natural Product ID	NPC31981
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	OXQKEKGBFMQTML-BIVRFLNRSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates [CHEMONTID:0002210] Sugar alcohols

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 30 29 0 0 0 0 0 0 0 0999 V2000 -3.5480 -0.1103 0.5733 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3307 -0.7099 -0.0797 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.0999 0.1701 0.1121 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0407 -0.4961 -0.6108 C 0 0 1 0 0 0 0 0 0 0 0 0 1.2991 0.3177 -0.6220 C 0 0 1 0 0 0 0 0 0 0 0 0 1.9446 0.4450 0.7327 C 0 0 2 0 0 0 0 0 0 0 0 0 3.2967 1.1368 0.5032 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9846 0.3472 -0.4182 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2519 -0.8218 1.2283 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2067 -0.3241 -1.4679 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2053 -1.7854 -0.1625 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 0.2148 1.4906 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5672 -0.7564 -1.4570 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7909 1.1694 0.1021 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4105 -0.7412 0.3021 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4710 -0.1470 1.6894 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1773 -1.7232 0.2871 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3130 1.1783 -0.2403 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2785 -0.5715 -1.6902 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0737 1.2992 -1.0692 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3464 0.9681 1.4740 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8685 1.1568 1.4603 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1593 2.1730 0.1517 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2349 0.8384 -1.2375 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0719 -1.1230 0.7516 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7015 -0.8353 -2.1485 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2093 -1.8846 0.8170 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2062 1.0469 1.9064 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2779 -1.6166 -1.8606 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5580 1.1845 -0.5175 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 1 0 7 8 1 0 6 9 1 0 5 10 1 0 4 11 1 0 3 12 1 0 2 13 1 0 1 14 1 0 1 15 1 0 1 16 1 0 2 17 1 1 3 18 1 6 4 19 1 6 5 20 1 6 6 21 1 1 7 22 1 0 7 23 1 0 8 24 1 0 9 25 1 0 10 26 1 0 11 27 1 0 12 28 1 0 13 29 1 0 14 30 1 0 M END

Standard InCHIKey	OXQKEKGBFMQTML-BIVRFLNRSA-N
Standard InCHI	InChI=1S/C7H16O7/c8-1-3(10)5(12)7(14)6(13)4(11)2-9/h3-14H,1-2H2/t3-,4+,5-,6-,7+/m1/s1
SMILES	C([C@H]([C@H]([C@@H]([C@@H]([C@H](CO)O)O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	212.09	Volume:	191.16 ? Van der Waals volume.
Dense:	1.109	LogP:	-2.093 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-1.819 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	0.18 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	0.0
TPSA:	141.61 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	7.0	Rings:	0.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.236	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.742	Fsp³:	1.0
MCE-18:	5.0 ? 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:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.023	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.025 ? 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:	0.514	Promiscuous compounds:	0.162

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.191	MDCK Permeability:	-4.493
Pgp-inhibitor:	0.0	Pgp-substrate:	0.322
PAMPA:	1.0 ? 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):	0.343
20% Bioavailability (F20%):	0.09	30% Bioavailability (F30%):	0.257
50% Bioavailability (F50%):	0.758

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.256	MRP1:	0.007
Plasma Protein Binding (PPB):	31.516%	Volume Distribution (VD):	-0.458
Fu:	75.748% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.994
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.036
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.009
CYP2C9-inhibitor:	0.674	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.002
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.938
HLM stability:	0.001 ? 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):

2.478

Half-life (T1/2):

1.863

ADMET: Toxicity

hERG Blockers:	0.005	hERG Blockers (10um):	0.029
Human Hepatotoxicity (H-HT):	0.334	Drug-induced Liver Injury (DILI):	0.002
AMES Toxicity:	0.529	Rat Oral Acute Toxicity:	0.002
Maximum Recommended Daily Dose:	0.001	Skin Sensitization:	0.55
Carcinogencity:	0.139	Eye Corrosion:	0.0
Eye Irritation:	0.278	Respiratory Toxicity:	0.0
Drug-induced Neurotoxicity:	0.001	Ototoxicity:	0.993
Hematotoxicity:	0.064	Drug-induced Nephrotoxicity:	0.403
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.038
A549 Cytotoxicity:	0.004	Hek293 Cytotoxicity:	0.008
BCF:	0.075 ? 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:	1.017 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	1.736 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	1.028 ? 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
NPO16886	Amorpha fruticosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18841906]
NPO21771	Citrus trifoliata	Species	Rutaceae	Eukaryota	n.a.	fruit	n.a.	PMID[23872723]
NPO16886	Amorpha fruticosa	Species	Fabaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[28075580]
NPO21771	Citrus trifoliata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32996318]
NPO16886	Amorpha fruticosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8326318]
NPO16886	Amorpha fruticosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8350086]
NPO16886	Amorpha fruticosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21771	Citrus trifoliata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23106	Piper solmsianum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9031	Euonymus europaeus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20824	Ecklonia kurome	Species	Lessoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24921	Acanthophyllum lilacinum	Species	Caryophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15647	Aloe ruspoliana	Species	Xanthorrhoeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12786	Dysoxylum beddomei	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17353	Iris brevicaulis	Species	Iridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22333	Operophtera brumata	Species	Geometridae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12601.1	Pueraria candollei var. mirifica	Varieties	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23106	Piper solmsianum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9031	Euonymus europaeus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO15647	Aloe ruspoliana	Species	Xanthorrhoeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO16886	Amorpha fruticosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO20824	Ecklonia kurome	Species	Lessoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21771	Citrus trifoliata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO9031	Euonymus europaeus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12601.1	Pueraria candollei var. mirifica	Varieties	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23106	Piper solmsianum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO15647	Aloe ruspoliana	Species	Xanthorrhoeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16886	Amorpha fruticosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO20824	Ecklonia kurome	Species	Lessoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16886	Amorpha fruticosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO21771	Citrus trifoliata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO20824	Ecklonia kurome	Species	Lessoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO12786	Dysoxylum beddomei	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23106	Piper solmsianum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17353	Iris brevicaulis	Species	Iridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24921	Acanthophyllum lilacinum	Species	Caryophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22333	Operophtera brumata	Species	Geometridae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15647	Aloe ruspoliana	Species	Xanthorrhoeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20824	Ecklonia kurome	Species	Lessoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9031	Euonymus europaeus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12601.1	Pueraria candollei var. mirifica	Varieties	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21771	Citrus trifoliata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16886	Amorpha fruticosa	Species	Fabaceae	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
Activity	2

Activity Type	# Activity
Cell line	2

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
NPT71	Cell line	HEK293	Homo sapiens	Activity	n.a.	n.a.	n.a.	PMID[37792632]

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 NPC31981 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	45865
0.1-0.2	3774
0.2-0.3	178
0.3-0.4	16
0.4-0.5	4
0.5-0.6	8
0.6-0.7	0
0.7-0.8	1
0.8-0.85	0
0.85-0.9	0
0.9-0.95	4
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9091	High Similarity	NPC293908
0.9091	High Similarity	NPC66052
0.9091	High Similarity	NPC192065
0.9091	High Similarity	NPC86412
0.75	Intermediate Similarity	NPC197207
0.75	Intermediate Similarity	NPC187058
0.75	Intermediate Similarity	NPC182541
0.75	Intermediate Similarity	NPC127074
0.75	Intermediate Similarity	NPC149070
0.5833	Remote Similarity	NPC301586
0.5833	Remote Similarity	NPC317060
0.5833	Remote Similarity	NPC33415
0.5556	Remote Similarity	NPC606151
0.5455	Remote Similarity	NPC227707
0.5455	Remote Similarity	NPC99573
0.5455	Remote Similarity	NPC102981
0.5455	Remote Similarity	NPC88278

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC31981 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	8702
0.1-0.2	365
0.2-0.3	52
0.3-0.4	12
0.4-0.5	7
0.5-0.6	5
0.6-0.7	0
0.7-0.8	1
0.8-0.85	0
0.85-0.9	0
0.9-0.95	3
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9091	High Similarity	NPD9051	Approved
0.9091	High Similarity	NPD9052	Phase 4
0.9091	High Similarity	NPD9053	Phase 4
0.75	Intermediate Similarity	NPD8814	Phase 3
0.5833	Remote Similarity	NPD8549	Clinical (unspecified phase)
0.5556	Remote Similarity	NPD9001	Phase 2
0.5556	Remote Similarity	NPD9002	Approved
0.5455	Remote Similarity	NPD8995	Clinical (unspecified phase)
0.5455	Remote Similarity	NPD8996	Phase 3

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