NPASS Compound

Natural Product: NPC275284

Natural Product ID	NPC275284
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Massonianoside B
IUPAC Name	(2S,3R,4R,5R,6S)-2-[4-[(2S,3R)-7-hydroxy-3-(hydroxymethyl)-5-(3-hydroxypropyl)-2,3-dihydro-1-benzofuran-2-yl]-2-methoxyphenoxy]-6-methyloxane-3,4,5-triol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2253066
PubChem CID	76311962
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0003405] 2-arylbenzofuran flavonoids

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 70 0 0 0 0 0 0 0 0999 V2000 5.9985 2.4303 0.1556 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3461 2.3435 0.4746 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0822 1.5246 -0.5466 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6036 0.1173 -0.6633 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1849 -0.0338 -1.0461 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1552 -0.1451 -0.1437 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8239 -0.2846 -0.5217 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5518 -0.4215 0.2346 C 0 0 2 0 0 0 0 0 0 0 0 0 2.7171 -1.5195 1.2938 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7387 -1.2099 2.1861 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6354 -0.9823 -0.8300 C 0 0 2 0 0 0 0 0 0 0 0 0 2.1304 -0.4589 -2.0239 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5063 -0.3142 -1.8813 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5572 -0.2008 -2.7904 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8701 -0.0633 -2.3922 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3153 -0.2225 -4.1576 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2212 -0.6676 -0.5804 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3213 0.5855 -0.7644 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6795 0.8215 -0.5084 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5214 -0.1729 -0.0678 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9617 -1.4434 0.1166 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6225 -1.6512 -0.1420 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8176 -2.4417 0.5614 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2578 -3.7297 0.7501 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8402 0.0203 0.1897 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6260 1.1517 0.0920 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.1790 1.5587 1.3054 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9105 0.5380 1.8963 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.4976 1.1061 3.1842 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9710 -0.0154 1.0106 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.0356 0.6115 -0.3518 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.6924 0.8978 -0.9508 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.8267 2.0197 -1.7744 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.8104 1.7702 -0.3688 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.8461 -1.4072 0.9162 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4421 2.7098 0.9210 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7954 3.3541 0.5886 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3825 1.8594 1.4901 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1834 1.5497 -0.3667 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9669 2.0000 -1.5660 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2663 -0.4482 -1.3821 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7987 -0.4115 0.3179 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3778 -0.1261 0.9257 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1987 0.5047 0.6856 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0021 -2.4711 0.8041 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7933 -1.6157 1.8919 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5629 -1.5464 3.1017 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7799 -2.0819 -0.8638 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6714 0.0234 -3.1320 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3910 0.0977 -4.4508 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3193 1.3770 -1.1082 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0575 1.8313 -0.6703 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2496 -2.6541 0.0195 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0438 -4.4800 0.9619 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7065 -4.0880 -0.1439 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5029 -3.6812 1.5691 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0113 2.0015 -0.2598 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2251 -0.2682 2.2034 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1728 1.9433 2.9999 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6533 1.4306 3.8195 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0181 0.2386 3.6759 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9661 0.1885 1.4984 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5714 -0.1237 -1.0146 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4059 0.0570 -1.6160 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3413 1.8428 -2.5779 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1280 1.8765 -1.3145 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8987 -1.6137 1.1311 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 2 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 8 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 14 16 1 0 11 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 21 23 1 0 23 24 1 0 20 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 28 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 31 34 1 0 30 35 1 0 15 5 1 0 22 17 1 0 32 26 1 0 13 7 2 0 1 36 1 0 2 37 1 0 2 38 1 0 3 39 1 0 3 40 1 0 4 41 1 0 4 42 1 0 6 43 1 0 8 44 1 1 9 45 1 0 9 46 1 0 10 47 1 0 11 48 1 6 15 49 1 0 16 50 1 0 18 51 1 0 19 52 1 0 22 53 1 0 24 54 1 0 24 55 1 0 24 56 1 0 26 57 1 6 28 58 1 1 29 59 1 0 29 60 1 0 29 61 1 0 30 62 1 1 31 63 1 6 32 64 1 6 33 65 1 0 34 66 1 0 35 67 1 0 M END

Standard InCHIKey	PHHIEOZUONPPQY-ROQFLNLZSA-N
Standard InCHI	InChI=1S/C25H32O10/c1-12-20(29)21(30)22(31)25(33-12)34-18-6-5-14(10-19(18)32-2)23-16(11-27)15-8-13(4-3-7-26)9-17(28)24(15)35-23/h5-6,8-10,12,16,20-23,25-31H,3-4,7,11H2,1-2H3/t12-,16-,20-,21+,22+,23+,25-/m0/s1
SMILES	OCCCc1cc2[C@H](CO)[C@H](Oc2c(c1)O)c1ccc(c(c1)OC)O[C@@H]1O[C@@H](C)[C@@H]([C@H]([C@H]1O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	492.2	Volume:	478.814 ? Van der Waals volume.
Dense:	1.028	LogP:	1.218 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.657 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.346 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	22.0
TPSA:	158.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	6.0	Rings:	4.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.31	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.328	Fsp³:	0.52
MCE-18:	87.579 ? 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:	0.582	Fluc inhibitor:	0.198 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.046 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.488 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.068	Promiscuous compounds:	0.077

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.864	MDCK Permeability:	-5.08
Pgp-inhibitor:	0.012	Pgp-substrate:	0.782
PAMPA:	0.979 ? 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):	0.324
20% Bioavailability (F20%):	0.327	30% Bioavailability (F30%):	0.835
50% Bioavailability (F50%):	0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.215
Plasma Protein Binding (PPB):	73.59%	Volume Distribution (VD):	-0.295
Fu:	25.833% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.928
OATP1B3 inhibitor:	0.968	BCRP inhibitor:	0.17
BSEP inhibitor:	0.341

ADMET: Metabolism

CYP1A2-inhibitor:	0.005	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.115	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.047	CYP3A4-substrate:	0.977
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.001 ? 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):

3.152

Half-life (T1/2):

3.075

ADMET: Toxicity

hERG Blockers:	0.098	hERG Blockers (10um):	0.25
Human Hepatotoxicity (H-HT):	0.765	Drug-induced Liver Injury (DILI):	0.537
AMES Toxicity:	0.655	Rat Oral Acute Toxicity:	0.016
Maximum Recommended Daily Dose:	0.02	Skin Sensitization:	0.945
Carcinogencity:	0.066	Eye Corrosion:	0.0
Eye Irritation:	0.474	Respiratory Toxicity:	0.022
Drug-induced Neurotoxicity:	0.007	Ototoxicity:	0.978
Hematotoxicity:	0.37	Drug-induced Nephrotoxicity:	0.769
Genotoxicity:	0.014	RPMI-8226 Immunitoxicity:	0.114
A549 Cytotoxicity:	0.307	Hek293 Cytotoxicity:	0.19
BCF:	0.455 ? 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:	3.099 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.813 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.865 ? 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
NPO15650	Picea neoveitchii	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22901896]
NPO15650	Picea neoveitchii	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15650	Picea neoveitchii	Species	Pinaceae	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
GI	5
IZ	4

Activity Type	# Activity
Organism	8
Non-molecular	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
NPT722	Organism	Athelia rolfsii	Athelia rolfsii	GI	=	0.0	%	PMID[21910504]
NPT1198	Organism	Magnaporthe grisea	Magnaporthe grisea	GI	=	37.6	%	PMID[16180824]
NPT722	Organism	Athelia rolfsii	Athelia rolfsii	IZ	=	0.0	mm	PMID[12477351]
NPT1198	Organism	Magnaporthe grisea	Magnaporthe grisea	IZ	=	7.0	mm	PMID[22342628]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	GI	=	17.9	%	PMID[22901896]
NPT1493	Organism	Ceratocystis paradoxa	Ceratocystis paradoxa	GI	=	21.8	%	DrugMatrix in vitro pharmacology data
NPT1494	Organism	Alternaria mali	Alternaria mali	GI	=	88.9	%	PMID[19908867]
NPT1493	Organism	Ceratocystis paradoxa	Ceratocystis paradoxa	IZ	=	5.6	mm	PMID[25978960]
NPT1494	Organism	Alternaria mali	Alternaria mali	IZ	=	8.8	mm	DrugMatrix in vivo data: Hematology

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 NPC275284 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	11049
0.1-0.2	34114
0.2-0.3	4155
0.3-0.4	477
0.4-0.5	52
0.5-0.6	5
0.6-0.7	4
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
0.7975	Intermediate Similarity	NPC31325
0.7895	Intermediate Similarity	NPC79429
0.679	Remote Similarity	NPC217635
0.6118	Remote Similarity	NPC471667
0.6071	Remote Similarity	NPC476301
0.6042	Remote Similarity	NPC316539
0.5465	Remote Similarity	NPC199539
0.5325	Remote Similarity	NPC230219
0.5325	Remote Similarity	NPC80600
0.5106	Remote Similarity	NPC15956
0.5055	Remote Similarity	NPC43508

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC275284 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3383
0.1-0.2	5592
0.2-0.3	169
0.3-0.4	6
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