NPASS Compound

Natural Product: NPC469686

Natural Product ID	NPC469686
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Aceroside Vii
IUPAC Name	(2R,3R,4S,5S,6R)-2-[(3R)-1,7-bis(4-hydroxyphenyl)heptan-3-yl]oxy-4,6-bis(hydroxymethyl)oxane-3,5-diol
Synonyms	Aceroside VII
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1098687
PubChem CID	46889080
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 70 72 0 0 0 0 0 0 0 0999 V2000 -4.1613 -0.3460 2.3838 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8852 -1.6359 1.9681 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3337 -1.8494 0.5124 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.6940 -0.9911 -0.3427 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3911 -1.2315 -0.6476 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6162 -0.4925 0.2443 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8624 0.5064 -0.4817 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.1498 1.8363 0.0694 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5353 2.9744 -0.6715 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8904 4.2906 -0.0158 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0143 5.0005 -0.3799 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3138 6.1957 0.2354 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5038 6.7236 1.2336 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3882 6.0124 1.5904 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0895 4.8030 0.9644 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8322 7.9373 1.8397 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5345 0.0231 -0.2121 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6967 0.7618 -0.7472 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9299 -0.1407 -0.3782 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1808 0.5154 -0.8809 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3173 -0.3636 -0.5136 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7481 -1.3624 -1.3664 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7943 -2.1839 -1.0495 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4684 -2.0410 0.1555 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0385 -1.0479 1.0011 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9802 -0.2146 0.6840 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5396 -2.8746 0.4907 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0144 -2.6730 -0.6295 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.1833 -3.5628 -0.9008 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.2516 -3.2861 0.1254 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.5012 -3.7178 -0.3080 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7902 -5.0168 -0.9418 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8895 -5.8124 -1.1941 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0521 -2.9724 -1.5990 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6112 -0.3213 3.2420 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8119 -1.8913 2.1022 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4373 -2.3211 2.6451 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4055 -1.5621 0.5209 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2024 -0.8320 -1.6859 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0600 0.4636 -1.5454 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6749 1.8687 1.1058 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2481 2.0484 0.1798 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5227 3.0050 -0.8413 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9983 3.0481 -1.7065 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6643 4.6166 -1.1532 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1871 6.7695 -0.0320 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2428 6.4199 2.3658 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8054 4.3020 1.2998 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8015 8.2522 1.8435 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6096 -1.0940 -0.4821 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6988 -0.0539 0.9260 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6954 1.0309 -1.7880 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9051 1.6706 -0.0989 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8763 -0.2093 0.7261 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7432 -1.1134 -0.8484 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3218 1.5254 -0.4948 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1187 0.4991 -1.9985 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2468 -1.5167 -2.3345 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1495 -2.9822 -1.7143 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5567 -0.9269 1.9443 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6440 0.5652 1.3504 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4697 -2.5598 0.2606 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5215 -2.8811 0.3444 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5905 -3.2967 -1.8968 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9987 -3.8750 1.0552 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1659 -2.9891 -0.2326 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0103 -5.1295 -1.7222 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3272 -5.3568 0.0073 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4493 -5.3979 -1.9100 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3253 -3.5392 -1.2626 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 32 33 1 0 28 34 1 0 30 3 1 0 15 10 1 0 26 21 1 0 1 35 1 0 2 36 1 0 2 37 1 0 3 38 1 1 5 39 1 6 7 40 1 6 8 41 1 0 8 42 1 0 9 43 1 0 9 44 1 0 11 45 1 0 12 46 1 0 14 47 1 0 15 48 1 0 16 49 1 0 17 50 1 0 17 51 1 0 18 52 1 0 18 53 1 0 19 54 1 0 19 55 1 0 20 56 1 0 20 57 1 0 22 58 1 0 23 59 1 0 25 60 1 0 26 61 1 0 27 62 1 0 28 63 1 1 29 64 1 6 30 65 1 1 31 66 1 0 32 67 1 0 32 68 1 0 33 69 1 0 34 70 1 0 M END

Standard InCHIKey	LUTXQCYAZCYAHY-DJZLDEFYSA-N
Standard InCHI	InChI=1S/C26H36O8/c27-15-22-24(31)23(16-28)34-26(25(22)32)33-21(14-9-18-7-12-20(30)13-8-18)4-2-1-3-17-5-10-19(29)11-6-17/h5-8,10-13,21-32H,1-4,9,14-16H2/t21-,22+,23-,24+,25-,26-/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)CO)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	476.24	Volume:	487.086 ? Van der Waals volume.
Dense:	0.978	LogP:	1.352 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.524 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.981 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	12.0	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:	0.255	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.976	Fsp³:	0.538
MCE-18:	61.75 ? 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:	0.511	Fluc inhibitor:	0.084 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.021 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.104 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.201	Promiscuous compounds:	0.06

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.159	MDCK Permeability:	-5.052
Pgp-inhibitor:	0.025	Pgp-substrate:	0.918
PAMPA:	0.758 ? 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):	0.0
20% Bioavailability (F20%):	0.026	30% Bioavailability (F30%):	0.998
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.034
Plasma Protein Binding (PPB):	87.616%	Volume Distribution (VD):	0.07
Fu:	12.415% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.951
OATP1B3 inhibitor:	0.973	BCRP inhibitor:	0.119
BSEP inhibitor:	0.968

ADMET: Metabolism

CYP1A2-inhibitor:	0.026	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	0.017	CYP2C19-substrate:	0.186
CYP2C9-inhibitor:	0.077	CYP2C9-substrate:	0.06
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.995
CYP3A4-inhibitor:	0.019	CYP3A4-substrate:	0.556
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.993
HLM stability:	0.884 ? 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):

4.237

Half-life (T1/2):

2.334

ADMET: Toxicity

hERG Blockers:	0.243	hERG Blockers (10um):	0.427
Human Hepatotoxicity (H-HT):	0.6	Drug-induced Liver Injury (DILI):	0.262
AMES Toxicity:	0.678	Rat Oral Acute Toxicity:	0.025
Maximum Recommended Daily Dose:	0.084	Skin Sensitization:	1.0
Carcinogencity:	0.128	Eye Corrosion:	0.001
Eye Irritation:	0.211	Respiratory Toxicity:	0.07
Drug-induced Neurotoxicity:	0.032	Ototoxicity:	0.956
Hematotoxicity:	0.246	Drug-induced Nephrotoxicity:	0.502
Genotoxicity:	0.002	RPMI-8226 Immunitoxicity:	0.049
A549 Cytotoxicity:	0.932	Hek293 Cytotoxicity:	0.936
BCF:	1.511 ? 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:	4.211 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.414 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.852 ? 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
NPO4138	Betula platyphylla	Species	Betulaceae	Eukaryota	bark	n.a.	n.a.	PMID[20363129]
NPO32876	alnus hirsuta f. sibirica	Species	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23465614]
NPO4138	Betula platyphylla	Species	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO32876	alnus hirsuta f. sibirica	Species	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4138	Betula platyphylla	Species	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4138	Betula platyphylla	Species	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4138	Betula platyphylla	Species	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO4138	Betula platyphylla	Species	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO4138	Betula platyphylla	Species	Betulaceae	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
Inhibition	4
Activity	3

Activity Type	# Activity
Cell line	5
Individual protein	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT641	Individual protein	Sodium/glucose cotransporter 2	Homo sapiens	Inhibition	=	14.1	%	PMID[26211462]
NPT640	Individual protein	Sodium/glucose cotransporter 1	Homo sapiens	Inhibition	=	9.7	%	PMID[26211462]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT521	Cell line	RBL-2H3	Rattus norvegicus	Inhibition	=	16.2	%	DrugMatrix in vitro pharmacology data
NPT521	Cell line	RBL-2H3	Rattus norvegicus	Inhibition	=	23.2	%	PMID[19191549]
NPT520	Cell line	3T3-L1	Mus musculus	Activity	=	93.6	%	PubChem BioAssay data set
NPT520	Cell line	3T3-L1	Mus musculus	Activity	=	93.2	%	PMID[21044847]
NPT520	Cell line	3T3-L1	Mus musculus	Activity	=	85.1	%	PMID[12398540]

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 NPC469686 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	15590
0.1-0.2	31573
0.2-0.3	2501
0.3-0.4	153
0.4-0.5	28
0.5-0.6	6
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
0.7	Intermediate Similarity	NPC201402
0.6087	Remote Similarity	NPC471067
0.5758	Remote Similarity	NPC264900
0.5333	Remote Similarity	NPC232454
0.5333	Remote Similarity	NPC470907
0.5333	Remote Similarity	NPC178449
0.5072	Remote Similarity	NPC94179
0.5065	Remote Similarity	NPC469687

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC469686 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4654
0.1-0.2	4380
0.2-0.3	115
0.3-0.4	1
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