NPASS Compound

Natural Product: NPC125041

Natural Product ID	NPC125041
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	YFVZKLQNMNKWSB-VFNWGFHPSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	443025
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0003686] Furanoid lignans [CHEMONTID:0001604] Tetrahydrofuran lignans [CHEMONTID:0003424] 9,9'-epoxylignans [CHEMONTID:0001613] Dibenzylbutyrolactone lignans

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 52 54 0 0 0 0 0 0 0 0999 V2000 6.9536 1.9661 1.6889 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3797 1.0717 0.7234 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0028 1.0206 0.5698 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1735 1.8280 1.3426 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8079 1.7538 1.1661 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2462 0.8946 0.2380 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7721 0.8090 0.0391 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2428 -0.2314 0.9758 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8117 -1.6006 0.7695 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1668 -2.4613 1.3551 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3642 -1.8013 1.5231 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4094 -2.1804 2.1280 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2321 -0.4873 0.8394 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6725 -0.6685 -0.5856 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1371 -0.9123 -0.5844 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6837 -2.1755 -0.4974 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0480 -2.3762 -0.4983 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9138 -1.3010 -0.5877 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3870 -0.0079 -0.6772 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0266 0.1556 -0.6735 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2617 1.0596 -0.7661 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7108 2.3602 -0.8557 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2845 -1.4388 -0.5933 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9587 0.5066 1.4919 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0957 0.1087 -0.5112 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4792 0.1530 -0.3642 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3102 -0.6575 -1.1401 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8360 -1.5520 -2.0982 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6234 2.9843 1.3627 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5496 1.6962 2.6793 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0452 1.8532 1.7238 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5885 2.5100 2.0771 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1300 2.3675 1.7500 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6239 0.5419 -1.0296 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3337 1.7890 0.2779 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4329 0.0698 2.0159 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8955 -1.8359 -0.3318 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7592 -1.7908 1.2814 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1682 -1.5791 -0.9791 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3810 0.1715 -1.2464 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0044 -3.0130 -0.4278 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4766 -3.3850 -0.4288 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5850 1.1508 -0.7420 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9924 2.5252 -0.0211 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5080 3.1291 -0.8729 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1787 2.4172 -1.8274 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8475 -0.8628 -1.1957 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5274 1.3697 1.2362 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7137 -0.5861 -1.2580 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6869 -2.1821 -2.4351 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3823 -0.9876 -2.9537 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0500 -2.1885 -1.6002 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 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 11 13 1 0 13 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 19 21 1 0 21 22 1 0 18 23 1 0 13 24 1 1 6 25 1 0 25 26 2 0 26 27 1 0 27 28 1 0 26 3 1 0 13 8 1 0 20 15 1 0 1 29 1 0 1 30 1 0 1 31 1 0 4 32 1 0 5 33 1 0 7 34 1 0 7 35 1 0 8 36 1 1 9 37 1 0 9 38 1 0 14 39 1 0 14 40 1 0 16 41 1 0 17 42 1 0 20 43 1 0 22 44 1 0 22 45 1 0 22 46 1 0 23 47 1 0 24 48 1 0 25 49 1 0 28 50 1 0 28 51 1 0 28 52 1 0 M END

Standard InCHIKey	YFVZKLQNMNKWSB-VFNWGFHPSA-N
Standard InCHI	InChI=1S/C21H24O7/c1-25-17-7-5-13(9-19(17)27-3)8-15-12-28-20(23)21(15,24)11-14-4-6-16(22)18(10-14)26-2/h4-7,9-10,15,22,24H,8,11-12H2,1-3H3/t15-,21+/m1/s1
SMILES	COc1ccc(C[C@@H]2COC(=O)[C@@]2(Cc2ccc(c(c2)OC)O)O)cc1OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	388.15	Volume:	389.179 ? Van der Waals volume.
Dense:	0.997	LogP:	1.628 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.908 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.158 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	18.0
TPSA:	94.45 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.702	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.266	Fsp³:	0.381
MCE-18:	64.138 ? 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:	1	PAINS Alert:	0
Colloidal aggregators:	0.088	Fluc inhibitor:	0.056 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.012 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.401 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.228	Promiscuous compounds:	0.131

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.105	MDCK Permeability:	-4.733
Pgp-inhibitor:	0.063	Pgp-substrate:	0.384
PAMPA:	0.129 ? 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):	0.001
20% Bioavailability (F20%):	0.599	30% Bioavailability (F30%):	0.315
50% Bioavailability (F50%):	0.845

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.974
Plasma Protein Binding (PPB):	91.277%	Volume Distribution (VD):	0.027
Fu:	8.504% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.027
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.96	CYP1A2-substrate:	0.977
CYP2C19-inhibitor:	0.999	CYP2C19-substrate:	0.998
CYP2C9-inhibitor:	0.133	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.007	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.994 ? 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):

6.321

Half-life (T1/2):

2.385

ADMET: Toxicity

hERG Blockers:	0.093	hERG Blockers (10um):	0.55
Human Hepatotoxicity (H-HT):	0.88	Drug-induced Liver Injury (DILI):	0.868
AMES Toxicity:	0.857	Rat Oral Acute Toxicity:	0.207
Maximum Recommended Daily Dose:	0.659	Skin Sensitization:	0.926
Carcinogencity:	0.768	Eye Corrosion:	0.002
Eye Irritation:	0.913	Respiratory Toxicity:	0.093
Drug-induced Neurotoxicity:	0.536	Ototoxicity:	0.527
Hematotoxicity:	0.685	Drug-induced Nephrotoxicity:	0.743
Genotoxicity:	0.991	RPMI-8226 Immunitoxicity:	0.133
A549 Cytotoxicity:	0.039	Hek293 Cytotoxicity:	0.414
BCF:	0.815 ? 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:	3.591 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.768 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.236 ? 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
NPO13014	Ipomoea cairica	Species	Convolvulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13014	Ipomoea cairica	Species	Convolvulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO13014	Ipomoea cairica	Species	Convolvulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13014	Ipomoea cairica	Species	Convolvulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO13014	Ipomoea cairica	Species	Convolvulaceae	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 NPC125041 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	16843
0.1-0.2	27964
0.2-0.3	4311
0.3-0.4	585
0.4-0.5	111
0.5-0.6	30
0.6-0.7	7
0.7-0.8	0
0.8-0.85	0
0.85-0.9	2
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC31751
0.8846	High Similarity	NPC253481
0.8846	High Similarity	NPC253722
0.7183	Intermediate Similarity	NPC163635
0.629	Remote Similarity	NPC300776
0.629	Remote Similarity	NPC176814
0.629	Remote Similarity	NPC4982
0.629	Remote Similarity	NPC606629
0.614	Remote Similarity	NPC607444
0.6071	Remote Similarity	NPC227217
0.6071	Remote Similarity	NPC117780
0.5588	Remote Similarity	NPC169973
0.5493	Remote Similarity	NPC478703
0.5493	Remote Similarity	NPC478704
0.5441	Remote Similarity	NPC487679
0.5441	Remote Similarity	NPC64201
0.5441	Remote Similarity	NPC487678
0.5439	Remote Similarity	NPC31344
0.5439	Remote Similarity	NPC317769
0.5362	Remote Similarity	NPC282291
0.5362	Remote Similarity	NPC166137
0.5323	Remote Similarity	NPC68779
0.5323	Remote Similarity	NPC108598
0.5323	Remote Similarity	NPC173308
0.5323	Remote Similarity	NPC181079
0.5323	Remote Similarity	NPC487680
0.5303	Remote Similarity	NPC110699
0.5303	Remote Similarity	NPC481088
0.5303	Remote Similarity	NPC106920
0.5303	Remote Similarity	NPC15811
0.5303	Remote Similarity	NPC23646
0.5303	Remote Similarity	NPC106055
0.5303	Remote Similarity	NPC485397
0.5224	Remote Similarity	NPC90431
0.5147	Remote Similarity	NPC485282
0.5147	Remote Similarity	NPC485283
0.5147	Remote Similarity	NPC485281
0.5143	Remote Similarity	NPC471988
0.5082	Remote Similarity	NPC5428
0.5079	Remote Similarity	NPC274356
0.5079	Remote Similarity	NPC101748

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC125041 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3810
0.1-0.2	5040
0.2-0.3	288
0.3-0.4	10
0.4-0.5	2
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