NPASS Compound

Natural Product: NPC533103

Natural Product ID	NPC533103
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[7-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-6,8-dimethoxy-4-oxochromen-5-yl]oxyoxan-2-yl]methyl acetate
IUPAC Name	[(2~{R},3~{S},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-[7-hydroxy-2-(3-hydroxy-4-methoxy-phenyl)-6,8-dimethoxy-4-oxo-chromen-5-yl]oxy-tetrahydropyran-2-yl]methyl acetate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 68 71 0 0 0 0 0 0 0 0999 V2000 9.7838 -1.0801 -0.9442 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7775 -2.0532 -0.8585 O 0 0 0 0 0 0 0 0 0 0 0 0 7.4467 -1.7512 -0.5956 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0775 -0.4334 -0.4072 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7477 -0.1071 -0.1421 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7812 -1.0883 -0.0635 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4120 -0.6822 0.2151 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3743 -1.5840 0.3227 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0751 -1.1733 0.5891 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1374 -1.9805 0.6917 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8376 0.1698 0.7449 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4290 0.6982 1.0179 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5200 -0.1006 1.1413 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3644 -0.4590 0.0641 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.3016 0.4965 -0.2025 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4853 0.2038 -0.8115 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.6013 1.1025 -0.3634 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8664 0.9063 -0.8400 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.8231 -0.0095 -0.6182 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.1601 -0.0124 -1.3169 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6202 -0.9238 0.2102 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7879 -1.2219 -1.0052 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.8840 -1.6868 -2.0244 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3609 -2.0109 0.2176 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.9000 -1.5846 1.3978 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8465 -1.8408 0.2168 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3896 -2.6871 -0.8257 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5713 2.0846 1.1686 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7777 2.7093 1.4404 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4530 3.3600 0.3838 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5151 2.9397 1.0508 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3423 4.3038 1.2049 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7346 2.4323 0.7861 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8497 3.2358 0.6572 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6216 3.5221 1.8296 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9094 1.0595 0.6320 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0851 0.5719 0.3810 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1618 -2.3733 -0.2509 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4896 -2.7320 -0.5187 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8754 -4.0444 -0.7099 O 0 0 0 0 0 0 0 0 0 0 0 0 10.7244 -1.6000 -1.2486 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5770 -0.2751 -1.6675 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9941 -0.6800 0.0796 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8298 0.3235 -0.4693 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5397 0.9410 -0.0072 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5285 -2.6459 0.2044 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6923 -0.4169 -0.8490 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3009 0.5849 -1.8946 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5771 1.2220 0.7677 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2911 2.1461 -0.7095 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7515 -0.8941 -1.0388 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7085 0.8710 -0.9125 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0402 0.1282 -2.3937 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7539 -1.4222 -1.4089 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2289 -2.5433 -2.3867 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5743 -3.0792 0.0519 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1799 -1.4968 2.0889 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5072 -2.3135 1.1587 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2526 -3.6035 -0.4752 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5481 3.2469 0.5108 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1862 2.9860 -0.6066 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1486 4.4296 0.4252 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9612 4.9200 0.6981 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9464 3.7941 2.6661 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1618 2.6006 2.1707 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3636 4.3125 1.6519 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4216 -3.1604 -0.1942 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7998 -4.5512 -1.5782 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 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 19 21 2 0 16 22 1 0 22 23 1 0 22 24 1 0 24 25 1 0 24 26 1 0 26 27 1 0 12 28 1 0 28 29 1 0 29 30 1 0 28 31 2 0 31 32 1 0 31 33 1 0 33 34 1 0 34 35 1 0 33 36 2 0 36 37 1 0 6 38 1 0 38 39 2 0 39 40 1 0 39 3 1 0 37 7 1 0 36 11 1 0 26 14 1 0 1 41 1 0 1 42 1 0 1 43 1 0 4 44 1 0 5 45 1 0 8 46 1 0 14 47 1 6 16 48 1 6 17 49 1 0 17 50 1 0 20 51 1 0 20 52 1 0 20 53 1 0 22 54 1 6 23 55 1 0 24 56 1 6 25 57 1 0 26 58 1 1 27 59 1 0 30 60 1 0 30 61 1 0 30 62 1 0 32 63 1 0 35 64 1 0 35 65 1 0 35 66 1 0 38 67 1 0 40 68 1 0 M END

Standard InCHIKey	FFHGFFUGZHGVBY-DKQWOSKQSA-N
Standard InCHI	InChI=1S/C26H28O14/c1-10(27)37-9-16-18(30)19(31)20(32)26(39-16)40-23-17-13(29)8-15(11-5-6-14(34-2)12(28)7-11)38-22(17)24(35-3)21(33)25(23)36-4/h5-8,16,18-20,26,28,30-33H,9H2,1-4H3/t16-,18-,19+,20-,26+/m1/s1
SMILES	COC1=CC=C(C2=CC(=O)C3=C(O[C@@H]4O[C@H](COC(C)=O)[C@@H](O)[C@H](O)[C@H]4O)C(OC)=C(O)C(OC)=C3O2)C=C1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	564.15	Volume:	523.361 ? Van der Waals volume.
Dense:	1.078	LogP:	0.753 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.147 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.086 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	25.0
TPSA:	203.81 ? Topological Polar Surface Area.	H-Bond Acceptor:	14.0
H-Bond Donor:	5.0	Rings:	4.0
Heavy Atoms:	14.0

MedChem Properties

QED Drug-Likeness Score:	0.238	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.22	Fsp³:	0.385
MCE-18:	95.056 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.485	Fluc inhibitor:	0.246 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.89 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.926 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.03	Promiscuous compounds:	0.304

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.011	MDCK Permeability:	-5.299
Pgp-inhibitor:	0.046	Pgp-substrate:	0.125
PAMPA:	0.42 ? 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):	0.257
20% Bioavailability (F20%):	0.47	30% Bioavailability (F30%):	0.977
50% Bioavailability (F50%):	0.981

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.062	MRP1:	0.398
Plasma Protein Binding (PPB):	85.536%	Volume Distribution (VD):	-0.386
Fu:	13.27% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.212
BSEP inhibitor:	0.587

ADMET: Metabolism

CYP1A2-inhibitor:	0.012	CYP1A2-substrate:	0.003
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.013	CYP2C9-substrate:	0.003
CYP2D6-inhibitor:	0.003	CYP2D6-substrate:	0.01
CYP3A4-inhibitor:	0.321	CYP3A4-substrate:	0.131
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.998
HLM stability:	0.864 ? 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):

2.121

Half-life (T1/2):

3.411

ADMET: Toxicity

hERG Blockers:	0.029	hERG Blockers (10um):	0.207
Human Hepatotoxicity (H-HT):	0.581	Drug-induced Liver Injury (DILI):	0.973
AMES Toxicity:	0.883	Rat Oral Acute Toxicity:	0.047
Maximum Recommended Daily Dose:	0.093	Skin Sensitization:	0.996
Carcinogencity:	0.505	Eye Corrosion:	0.0
Eye Irritation:	0.214	Respiratory Toxicity:	0.025
Drug-induced Neurotoxicity:	0.026	Ototoxicity:	0.719
Hematotoxicity:	0.399	Drug-induced Nephrotoxicity:	0.496
Genotoxicity:	0.59	RPMI-8226 Immunitoxicity:	0.142
A549 Cytotoxicity:	0.273	Hek293 Cytotoxicity:	0.337
BCF:	0.387 ? 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:	3.025 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.482 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.858 ? 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
NPO14602	Vitex negundo	Species	Lamiaceae	Eukaryota	leaves	n.a.	n.a.	PMID[12828478]
NPO14602	Vitex negundo	Species	Lamiaceae	Eukaryota	n.a.	root	n.a.	PMID[15520511]
NPO14602	Vitex negundo	Species	Lamiaceae	Eukaryota	seeds	n.a.	n.a.	PMID[15620254]
NPO14602	Vitex negundo	Species	Lamiaceae	Eukaryota	seeds	n.a.	n.a.	PMID[1624939]
NPO14602	Vitex negundo	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17027268]
NPO14602	Vitex negundo	Species	Lamiaceae	Eukaryota	Seeds	n.a.	n.a.	PMID[19715321]
NPO14602	Vitex negundo	Species	Lamiaceae	Eukaryota	Seeds	n.a.	n.a.	PMID[19931461]
NPO14602	Vitex negundo	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23403897]
NPO14602	Vitex negundo	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38163555]
NPO14602	Vitex negundo	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14602	Vitex negundo	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14602	Vitex negundo	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO14602	Vitex negundo	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO14602	Vitex negundo	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO14602	Vitex negundo	Species	Lamiaceae	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 NPC533103 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	15829
0.1-0.2	30449
0.2-0.3	2757
0.3-0.4	668
0.4-0.5	144
0.5-0.6	8
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
0.6022	Remote Similarity	NPC254540
0.5914	Remote Similarity	NPC211594
0.5758	Remote Similarity	NPC209296
0.5745	Remote Similarity	NPC172807
0.5152	Remote Similarity	NPC609888
0.5104	Remote Similarity	NPC22832
0.5104	Remote Similarity	NPC605067
0.5104	Remote Similarity	NPC606560
0.5098	Remote Similarity	NPC153755

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC533103 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4400
0.1-0.2	4672
0.2-0.3	66
0.3-0.4	10
0.4-0.5	0
0.5-0.6	2
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
0.5758	Remote Similarity	NPD7054	Phase 4
0.5728	Remote Similarity	NPD7472	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