NPASS Compound

Natural Product: NPC201402

Natural Product ID	NPC201402
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(3R)-1,7-Bis-(3,4-Dihydroxyphenyl)-3-Heptanol-3-O-Beta-D-Glucopyranoside
IUPAC Name	(2R,3R,4S,5S,6R)-2-[(3R)-1,7-bis(4-hydroxyphenyl)heptan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2346805
PubChem CID	21637601
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002650] Diarylheptanoids [CHEMONTID:0002651] Linear diarylheptanoids

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 67 69 0 0 0 0 0 0 0 0999 V2000 -2.7963 -1.9119 2.6759 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9398 -2.4142 2.0614 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6651 -2.6478 0.5739 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.3190 -1.4494 0.0040 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0159 -1.3669 -0.4534 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.1582 -1.2983 0.6181 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4712 0.0093 0.6213 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9018 0.6116 1.9078 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5389 1.9212 2.3925 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9510 3.1111 1.6226 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1165 3.8186 0.8126 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6005 4.9219 0.0982 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8981 5.3415 0.1701 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7488 4.6317 0.9881 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2886 3.5436 1.6972 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3893 6.4354 -0.5347 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9794 -0.3403 0.4901 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9647 0.7387 0.3397 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8261 1.5099 -0.9611 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1075 0.6378 -2.1639 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4990 0.1047 -2.1794 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8388 -1.1015 -1.6391 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1510 -1.5501 -1.6748 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1685 -0.8170 -2.2478 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7948 0.3965 -2.7852 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5084 0.8684 -2.7663 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4840 -1.2455 -2.2943 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6149 -2.4713 -1.3731 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0627 -3.8331 -0.9057 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.6006 -3.7121 0.5050 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.1865 -4.9053 0.9318 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0778 -4.7896 -1.0097 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1017 -2.2546 -2.6734 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2462 -2.6301 3.0752 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1390 -3.4149 2.5358 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7669 -1.7179 2.2156 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6285 -3.0443 0.1575 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9879 -0.4182 -1.0714 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8455 0.5226 -0.2329 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0579 0.6023 1.8485 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6412 -0.1441 2.7300 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5229 2.0263 2.7602 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1013 2.0709 3.4005 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9212 3.5421 0.7339 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0736 5.4606 -0.5314 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7809 4.9508 1.0572 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0015 3.0314 2.3180 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8572 7.2975 -0.5095 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3061 -1.0151 1.3374 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0489 -1.0209 -0.4092 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9815 0.2294 0.2360 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0596 1.4779 1.1286 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5340 2.3601 -0.9583 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7994 1.9607 -1.0580 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3963 -0.2027 -2.1846 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9587 1.3061 -3.0523 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1188 -1.7400 -1.1781 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4396 -2.5126 -1.2469 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5685 1.0161 -3.2523 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2511 1.8448 -3.2076 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2828 -0.6122 -2.1534 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5119 -2.4821 -1.4708 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9230 -4.1378 -1.5357 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7571 -3.5085 1.1784 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1529 -4.9496 0.7015 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0785 -5.2109 -1.9248 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6649 -1.4314 -2.7035 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 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 13 16 1 0 7 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 24 27 1 0 5 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 29 32 1 0 28 33 1 0 30 3 1 0 15 10 1 0 26 21 1 0 1 34 1 0 2 35 1 0 2 36 1 0 3 37 1 6 5 38 1 6 7 39 1 6 8 40 1 0 8 41 1 0 9 42 1 0 9 43 1 0 11 44 1 0 12 45 1 0 14 46 1 0 15 47 1 0 16 48 1 0 17 49 1 0 17 50 1 0 18 51 1 0 18 52 1 0 19 53 1 0 19 54 1 0 20 55 1 0 20 56 1 0 22 57 1 0 23 58 1 0 25 59 1 0 26 60 1 0 27 61 1 0 28 62 1 6 29 63 1 6 30 64 1 1 31 65 1 0 32 66 1 0 33 67 1 0 M END

Standard InCHIKey	MAUAGULXOHJIER-RRLSKXGXSA-N
Standard InCHI	InChI=1S/C25H34O8/c26-15-21-22(29)23(30)24(31)25(33-21)32-20(14-9-17-7-12-19(28)13-8-17)4-2-1-3-16-5-10-18(27)11-6-16/h5-8,10-13,20-31H,1-4,9,14-15H2/t20-,21-,22-,23+,24-,25-/m1/s1
SMILES	OC[C@H]1O[C@@H](O[C@@H](CCc2ccc(cc2)O)CCCCc2ccc(cc2)O)[C@@H]([C@H]([C@@H]1O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	462.23	Volume:	469.79 ? Van der Waals volume.
Dense:	0.984	LogP:	1.539 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.62 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.839 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	18.0
TPSA:	139.84 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	6.0	Rings:	3.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.277	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.791	Fsp³:	0.52
MCE-18:	62.0 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.555	Fluc inhibitor:	0.152 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.031 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.078 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.206	Promiscuous compounds:	0.143

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.205	MDCK Permeability:	-5.079
Pgp-inhibitor:	0.006	Pgp-substrate:	0.724
PAMPA:	0.895 ? 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):	0.021
20% Bioavailability (F20%):	0.203	30% Bioavailability (F30%):	0.993
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.025
Plasma Protein Binding (PPB):	90.07%	Volume Distribution (VD):	0.019
Fu:	9.952% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.997
OATP1B3 inhibitor:	0.991	BCRP inhibitor:	0.174
BSEP inhibitor:	0.859

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.093
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.556
CYP2D6-inhibitor:	0.99	CYP2D6-substrate:	0.874
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.29
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.991
HLM stability:	0.737 ? 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):

3.368

Half-life (T1/2):

1.704

ADMET: Toxicity

hERG Blockers:	0.343	hERG Blockers (10um):	0.789
Human Hepatotoxicity (H-HT):	0.571	Drug-induced Liver Injury (DILI):	0.455
AMES Toxicity:	0.29	Rat Oral Acute Toxicity:	0.019
Maximum Recommended Daily Dose:	0.089	Skin Sensitization:	0.997
Carcinogencity:	0.035	Eye Corrosion:	0.001
Eye Irritation:	0.322	Respiratory Toxicity:	0.062
Drug-induced Neurotoxicity:	0.043	Ototoxicity:	0.929
Hematotoxicity:	0.047	Drug-induced Nephrotoxicity:	0.763
Genotoxicity:	0.007	RPMI-8226 Immunitoxicity:	0.06
A549 Cytotoxicity:	0.806	Hek293 Cytotoxicity:	0.907
BCF:	1.69 ? 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:	4.566 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.598 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.145 ? 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
NPO32876	alnus hirsuta f. sibirica	Species	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23465614]
NPO32876	alnus hirsuta f. sibirica	Species	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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	3
IC50	1
Inhibition	1
ID50	1

Activity Type	# Activity
Cell line	5
Organism	1

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
NPT520	Cell line	3T3-L1	Mus musculus	Activity	=	98.1	%	PubChem BioAssay data set
NPT520	Cell line	3T3-L1	Mus musculus	Activity	=	103.1	%	PMID[21044847]
NPT520	Cell line	3T3-L1	Mus musculus	Activity	=	76.0	%	PMID[12398540]
NPT1182	Cell line	J774.A1	Mus musculus	IC50	=	100000.0	nM	PMID[33422907]
NPT113	Cell line	RAW264.7	Mus musculus	Inhibition	=	24.0	%	PMID[33422907]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT32	Organism	Mus musculus	Mus musculus	ID50	=	0.66	mg	PMID[33422907]

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 NPC201402 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	18421
0.1-0.2	26132
0.2-0.3	4504
0.3-0.4	701
0.4-0.5	62
0.5-0.6	20
0.6-0.7	7
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8214	Intermediate Similarity	NPC264900
0.7869	Intermediate Similarity	NPC471067
0.7241	Intermediate Similarity	NPC160854
0.7241	Intermediate Similarity	NPC17968
0.7241	Intermediate Similarity	NPC469705
0.7241	Intermediate Similarity	NPC469704
0.7241	Intermediate Similarity	NPC469703
0.7222	Intermediate Similarity	NPC148055
0.7	Intermediate Similarity	NPC469686
0.6866	Remote Similarity	NPC232454
0.6866	Remote Similarity	NPC470907
0.6866	Remote Similarity	NPC178449
0.6765	Remote Similarity	NPC184092
0.6562	Remote Similarity	NPC79715
0.6562	Remote Similarity	NPC108659
0.6	Remote Similarity	NPC199459
0.5938	Remote Similarity	NPC94179
0.5938	Remote Similarity	NPC231607
0.5938	Remote Similarity	NPC293686
0.5882	Remote Similarity	NPC471066
0.5846	Remote Similarity	NPC282409
0.5846	Remote Similarity	NPC469702
0.5833	Remote Similarity	NPC602133
0.5593	Remote Similarity	NPC157338
0.5571	Remote Similarity	NPC254275
0.5429	Remote Similarity	NPC52277
0.5405	Remote Similarity	NPC469687
0.5231	Remote Similarity	NPC158673
0.5211	Remote Similarity	NPC471095
0.5205	Remote Similarity	NPC164172
0.5085	Remote Similarity	NPC175771
0.5079	Remote Similarity	NPC200988
0.5079	Remote Similarity	NPC145023
0.507	Remote Similarity	NPC476448
0.507	Remote Similarity	NPC469548
0.507	Remote Similarity	NPC476445

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC201402 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5162
0.1-0.2	3801
0.2-0.3	166
0.3-0.4	21
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