NPASS Compound

Natural Product: NPC475942

Natural Product ID	NPC475942
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Alternanthin
IUPAC Name	6-[(2S,4R,5S,6S)-4,5-dihydroxy-6-methyloxan-2-yl]oxy-5,7-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)chromen-4-one
Synonyms	Alternanthin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL519071
PubChem CID	44559262
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001111] Flavonoid glycosides [CHEMONTID:0001583] Flavonoid O-glycosides

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 54 57 0 0 0 0 0 0 0 0999 V2000 6.5125 -1.1838 4.2346 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2854 -0.9288 3.0743 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6773 -0.6390 1.8462 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2806 -0.6167 1.8329 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6559 -0.3421 0.6628 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3759 -0.0860 -0.5075 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7378 -0.1150 -0.4605 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4236 -0.3922 0.7183 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7989 -0.4333 0.8167 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1925 -0.3035 0.5912 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4207 -0.5251 1.7000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0340 -0.4690 1.5352 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2587 -0.6600 2.4991 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4991 -0.1976 0.2845 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3477 0.0174 -0.7971 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6233 -0.0450 -0.5920 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7907 0.2848 -2.0357 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5784 0.3391 -2.2104 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4346 0.1288 -1.1534 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8539 -0.1343 0.0685 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6843 -0.3515 1.1660 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8023 0.1836 -1.3401 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6041 1.3188 -1.2482 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.4956 1.5530 -2.4128 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7571 0.7404 -2.4103 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.5997 -0.4711 -3.0726 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.2987 0.4874 -1.0269 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.1055 0.0465 -0.1888 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.3163 1.1830 -0.0285 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5367 -0.5327 1.1396 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7214 1.7141 -0.5137 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1136 0.6062 -3.4575 O 0 0 0 0 0 0 0 0 0 0 0 0 5.9328 -0.2606 4.4535 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8019 -2.0148 4.0324 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1694 -1.4472 5.0617 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7564 -0.8178 2.7493 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8463 0.1301 -1.4414 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3571 0.0793 -1.3479 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2918 -1.3366 0.8290 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8407 -0.7375 2.6654 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4434 0.4533 -2.9000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1461 0.3783 1.6722 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0094 2.2652 -1.0813 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9142 1.2472 -3.3337 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7237 2.6276 -2.5725 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5353 1.3061 -2.9753 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0727 -1.2110 -2.5834 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0757 -0.2736 -1.0874 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5702 -0.7088 -0.8296 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2026 0.1039 1.9918 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0067 -1.5048 1.2514 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6144 -0.7593 1.1826 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6924 1.8674 -0.7011 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8887 0.0122 -3.7493 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 2 0 8 9 1 0 5 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 2 0 15 16 1 0 15 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 19 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 25 27 1 0 27 28 1 0 28 29 1 0 28 30 1 0 27 31 1 0 18 32 1 0 8 3 1 0 16 10 1 0 29 23 1 0 20 14 1 0 1 33 1 0 1 34 1 0 1 35 1 0 4 36 1 0 6 37 1 0 7 38 1 0 9 39 1 0 11 40 1 0 17 41 1 0 21 42 1 0 23 43 1 1 24 44 1 0 24 45 1 0 25 46 1 6 26 47 1 0 27 48 1 6 28 49 1 6 30 50 1 0 30 51 1 0 30 52 1 0 31 53 1 0 32 54 1 0 M END

Standard InCHIKey	LORQHSFIQJBWBT-DKVFDIBASA-N
Standard InCHI	InChI=1S/C22H22O10/c1-9-20(27)13(25)8-18(30-9)32-22-14(26)7-17-19(21(22)28)12(24)6-15(31-17)10-3-4-11(23)16(5-10)29-2/h3-7,9,13,18,20,23,25-28H,8H2,1-2H3/t9-,13+,18-,20+/m0/s1
SMILES	COc1cc(ccc1O)c1cc(=O)c2c(o1)cc(c(c2O)O[C@H]1C[C@@H](O)[C@@H]([C@@H](O1)C)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	446.12	Volume:	421.653 ? Van der Waals volume.
Dense:	1.058	LogP:	1.582 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.839 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.717 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	24.0
TPSA:	159.05 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	5.0	Rings:	4.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.4	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.004	Fsp³:	0.318
MCE-18:	86.966 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.65	Fluc inhibitor:	0.316 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.966 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.841 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.093	Promiscuous compounds:	0.715

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.796	MDCK Permeability:	-5.009
Pgp-inhibitor:	0.004	Pgp-substrate:	0.774
PAMPA:	0.94 ? 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):	0.056
20% Bioavailability (F20%):	0.817	30% Bioavailability (F30%):	0.962
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.888
Plasma Protein Binding (PPB):	92.45%	Volume Distribution (VD):	-0.172
Fu:	6.782% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.974
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.972
BSEP inhibitor:	0.519

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.018
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.003
CYP2C9-inhibitor:	0.068	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.267	CYP2D6-substrate:	0.829
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.217 ? 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):

5.068

Half-life (T1/2):

2.536

ADMET: Toxicity

hERG Blockers:	0.084	hERG Blockers (10um):	0.4
Human Hepatotoxicity (H-HT):	0.624	Drug-induced Liver Injury (DILI):	0.887
AMES Toxicity:	0.745	Rat Oral Acute Toxicity:	0.486
Maximum Recommended Daily Dose:	0.941	Skin Sensitization:	0.89
Carcinogencity:	0.451	Eye Corrosion:	0.002
Eye Irritation:	0.93	Respiratory Toxicity:	0.62
Drug-induced Neurotoxicity:	0.026	Ototoxicity:	0.418
Hematotoxicity:	0.094	Drug-induced Nephrotoxicity:	0.205
Genotoxicity:	0.942	RPMI-8226 Immunitoxicity:	0.213
A549 Cytotoxicity:	0.534	Hek293 Cytotoxicity:	0.574
BCF:	0.671 ? 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:	3.413 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.502 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.853 ? 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
NPO7863	Dioscorea opposita	Species	Dioscoreaceae	Eukaryota	aerial parts	n.a.	n.a.	PMID[16124773]
NPO7863	Dioscorea opposita	Species	Dioscoreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7863	Dioscorea opposita	Species	Dioscoreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7863	Dioscorea opposita	Species	Dioscoreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO7863	Dioscorea opposita	Species	Dioscoreaceae	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	9

Activity Type	# Activity
Tissue	6
Others	3

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
NPT632	Tissue	Brain	Rattus norvegicus	Activity	=	1.4	mmol	PMID[26034885]
NPT632	Tissue	Brain	Rattus norvegicus	Activity	=	1.34	mmol	PMID[26034885]
NPT632	Tissue	Brain	Rattus norvegicus	Activity	=	1.57	mmol	PMID[12161151]
NPT2	Others	Unspecified	n.a.	Activity	=	25.08	%	PMID[18973387]
NPT2	Others	Unspecified	n.a.	Activity	=	28.29	%	PMID[18973387]
NPT2	Others	Unspecified	n.a.	Activity	=	38.12	%	PMID[18973387]
NPT2535	Tissue	Plasma	Oryctolagus cuniculus	Activity	=	70.27	%	PMID[17985844]
NPT2535	Tissue	Plasma	Oryctolagus cuniculus	Activity	=	96.06	%	PMID[25981689]
NPT2535	Tissue	Plasma	Oryctolagus cuniculus	Activity	=	129.42	%	PMID[25981689]

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 NPC475942 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	13149
0.1-0.2	33008
0.2-0.3	2785
0.3-0.4	721
0.4-0.5	163
0.5-0.6	29
0.6-0.7	2
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
0.6912	Remote Similarity	NPC83508
0.6386	Remote Similarity	NPC606560
0.5811	Remote Similarity	NPC47781
0.5775	Remote Similarity	NPC241498
0.5747	Remote Similarity	NPC602805
0.56	Remote Similarity	NPC183950
0.5556	Remote Similarity	NPC284552
0.5521	Remote Similarity	NPC195257
0.5479	Remote Similarity	NPC100887
0.5417	Remote Similarity	NPC293183
0.5405	Remote Similarity	NPC312924
0.5393	Remote Similarity	NPC311830
0.5342	Remote Similarity	NPC156222
0.5333	Remote Similarity	NPC255350
0.5281	Remote Similarity	NPC101026
0.5281	Remote Similarity	NPC488077
0.5281	Remote Similarity	NPC601710
0.5275	Remote Similarity	NPC4390
0.5263	Remote Similarity	NPC4455
0.5222	Remote Similarity	NPC223747
0.5222	Remote Similarity	NPC111249
0.52	Remote Similarity	NPC256283
0.5195	Remote Similarity	NPC137062
0.5195	Remote Similarity	NPC606105
0.5185	Remote Similarity	NPC470402
0.5181	Remote Similarity	NPC602497
0.5132	Remote Similarity	NPC280339
0.5132	Remote Similarity	NPC20830
0.5114	Remote Similarity	NPC305811
0.5104	Remote Similarity	NPC472992
0.5065	Remote Similarity	NPC115323

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC475942 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4249
0.1-0.2	4823
0.2-0.3	70
0.3-0.4	6
0.4-0.5	1
0.5-0.6	1
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
0.5333	Remote Similarity	NPD2801	Pre-clinical

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