NPASS Compound

Natural Product: NPC327032

Natural Product ID	NPC327032
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Saccharumoside B
IUPAC Name	[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[4-(hydroxymethyl)-2-methoxyphenoxy]oxan-2-yl]methyl 4-hydroxy-3-methoxybenzoate
Synonyms	Saccharumoside B
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1923079
PubChem CID	56834590
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000238] Tannins [CHEMONTID:0001710] Hydrolyzable tannins

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 59 61 0 0 0 0 0 0 0 0999 V2000 8.1268 1.8253 -2.0521 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3679 2.3950 -1.0371 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2536 1.5215 -0.6026 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4404 0.6149 0.4084 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4140 -0.1969 0.8161 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1301 -0.1605 0.2434 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9643 0.7597 -0.7729 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0095 1.5853 -1.1868 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7466 0.8854 -1.4098 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5946 1.8285 -2.4437 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1867 -0.9960 0.7101 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8859 -1.2750 0.4544 C 0 0 2 0 0 0 0 0 0 0 0 0 1.0271 -1.0723 1.5519 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2754 -0.9335 0.9907 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.0951 -0.1168 1.9079 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4043 0.1050 1.5985 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4039 -0.8208 1.7023 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2617 -1.9917 2.1164 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7669 -0.4189 1.2959 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8022 -1.3076 1.3803 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0812 -0.9240 0.9967 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3317 0.3497 0.5269 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2923 1.2411 0.4425 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0212 0.8364 0.8314 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5052 2.5276 -0.0240 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4204 3.4304 -0.1031 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6289 0.6995 0.1508 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8051 -2.1528 0.3765 C 0 0 2 0 0 0 0 0 0 0 0 0 0.2460 -2.6899 -0.6115 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6137 -2.7106 0.0307 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5469 -3.1893 -0.8512 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1276 -3.9035 -1.1256 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8668 -1.7730 -0.4842 O 0 0 0 0 0 0 0 0 0 0 0 0 8.0307 2.3939 -2.8706 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0619 2.5013 -0.1587 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9659 3.3928 -1.3133 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4345 0.5811 0.8576 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5691 -0.8969 1.6012 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8729 2.3025 -1.9820 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3459 1.5836 -3.2478 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5713 1.8803 -2.8306 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8867 2.8428 -2.0486 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4845 -0.6486 -0.3597 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0420 -0.2162 0.1059 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5821 0.8958 2.0076 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9588 -0.5442 2.9495 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6136 -2.2960 1.7437 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8897 -1.6312 1.0670 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2028 1.5312 0.7673 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7028 4.3671 -0.5984 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6013 2.9313 -0.6667 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0782 3.6751 0.9297 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2686 1.0179 0.8669 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0722 -2.9464 1.0691 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2857 -1.9476 -1.4355 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5503 -3.3833 0.9143 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7175 -4.1581 -0.7209 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0118 -4.6609 -0.5032 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2405 -2.5392 -0.9570 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 7 9 1 0 9 10 1 0 6 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 2 0 17 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 1 0 22 27 1 0 14 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 29 32 1 0 28 33 1 0 8 3 1 0 30 12 1 0 24 19 1 0 1 34 1 0 2 35 1 0 2 36 1 0 4 37 1 0 5 38 1 0 8 39 1 0 10 40 1 0 10 41 1 0 10 42 1 0 12 43 1 6 14 44 1 6 15 45 1 0 15 46 1 0 20 47 1 0 21 48 1 0 24 49 1 0 26 50 1 0 26 51 1 0 26 52 1 0 27 53 1 0 28 54 1 1 29 55 1 6 30 56 1 1 31 57 1 0 32 58 1 0 33 59 1 0 M END

Standard InCHIKey	XDCJBRVCYFCQAN-OUUKCGNVSA-N
Standard InCHI	InChI=1S/C22H26O11/c1-29-15-8-12(4-5-13(15)24)21(28)31-10-17-18(25)19(26)20(27)22(33-17)32-14-6-3-11(9-23)7-16(14)30-2/h3-8,17-20,22-27H,9-10H2,1-2H3/t17-,18-,19+,20-,22-/m1/s1
SMILES	OCc1ccc(c(c1)OC)O[C@@H]1O[C@H](COC(=O)c2ccc(c(c2)OC)O)[C@H]([C@@H]([C@H]1O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	466.15	Volume:	441.636 ? Van der Waals volume.
Dense:	1.056	LogP:	0.563 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.868 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.161 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	19.0
TPSA:	164.37 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	5.0	Rings:	3.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.331	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.592	Fsp³:	0.409
MCE-18:	69.774 ? 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:	0.476	Fluc inhibitor:	0.13 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.122 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.468 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.118	Promiscuous compounds:	0.232

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.229	MDCK Permeability:	-5.337
Pgp-inhibitor:	0.006	Pgp-substrate:	0.076
PAMPA:	0.351 ? 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):	0.098
20% Bioavailability (F20%):	0.723	30% Bioavailability (F30%):	0.95
50% Bioavailability (F50%):	0.974

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.047	MRP1:	0.49
Plasma Protein Binding (PPB):	70.68%	Volume Distribution (VD):	-0.106
Fu:	30.082% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.071
BSEP inhibitor:	0.401

ADMET: Metabolism

CYP1A2-inhibitor:	0.003	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.057	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.011	CYP2C9-substrate:	0.012
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.025
CYP3A4-inhibitor:	0.009	CYP3A4-substrate:	0.756
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.996
HLM stability:	0.235 ? 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):

3.047

Half-life (T1/2):

2.48

ADMET: Toxicity

hERG Blockers:	0.041	hERG Blockers (10um):	0.401
Human Hepatotoxicity (H-HT):	0.194	Drug-induced Liver Injury (DILI):	0.64
AMES Toxicity:	0.464	Rat Oral Acute Toxicity:	0.017
Maximum Recommended Daily Dose:	0.038	Skin Sensitization:	0.841
Carcinogencity:	0.32	Eye Corrosion:	0.0
Eye Irritation:	0.734	Respiratory Toxicity:	0.049
Drug-induced Neurotoxicity:	0.082	Ototoxicity:	0.61
Hematotoxicity:	0.045	Drug-induced Nephrotoxicity:	0.497
Genotoxicity:	0.105	RPMI-8226 Immunitoxicity:	0.159
A549 Cytotoxicity:	0.148	Hek293 Cytotoxicity:	0.194
BCF:	0.354 ? 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:	3.062 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.445 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.743 ? 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
NPO14559	Acer saccharum	Species	Sapindaceae	Eukaryota	n.a.	bark	n.a.	PMID[22032697]
NPO14559	Acer saccharum	Species	Sapindaceae	Eukaryota	bark	n.a.	n.a.	PMID[22032697]
NPO14559	Acer saccharum	Species	Sapindaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14559	Acer saccharum	Species	Sapindaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14559	Acer saccharum	Species	Sapindaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO14559	Acer saccharum	Species	Sapindaceae	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
IC50	2

Activity Type	# Activity
Cell line	2

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
NPT393	Cell line	HCT-116	Homo sapiens	IC50	<	5.0	ug.mL-1	PMID[22032697]
NPT492	Cell line	Caco-2	Homo sapiens	IC50	<	5.0	ug.mL-1	PMID[22032697]

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 NPC327032 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	12961
0.1-0.2	31745
0.2-0.3	4180
0.3-0.4	818
0.4-0.5	115
0.5-0.6	25
0.6-0.7	6
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
0.7727	Intermediate Similarity	NPC111785
0.7429	Intermediate Similarity	NPC311803
0.7361	Intermediate Similarity	NPC5786
0.7286	Intermediate Similarity	NPC160780
0.6986	Remote Similarity	NPC102851
0.6944	Remote Similarity	NPC197708
0.6301	Remote Similarity	NPC119125
0.625	Remote Similarity	NPC658
0.6111	Remote Similarity	NPC316539
0.6081	Remote Similarity	NPC25821
0.5946	Remote Similarity	NPC25389
0.575	Remote Similarity	NPC485234
0.5679	Remote Similarity	NPC194095
0.5672	Remote Similarity	NPC166040
0.561	Remote Similarity	NPC471405
0.5604	Remote Similarity	NPC163165
0.5556	Remote Similarity	NPC65833
0.5526	Remote Similarity	NPC1913
0.5467	Remote Similarity	NPC166277
0.5455	Remote Similarity	NPC4958
0.5395	Remote Similarity	NPC472859
0.5287	Remote Similarity	NPC476011
0.5256	Remote Similarity	NPC215811
0.525	Remote Similarity	NPC36130
0.52	Remote Similarity	NPC484156
0.5185	Remote Similarity	NPC18979
0.5181	Remote Similarity	NPC472860
0.5181	Remote Similarity	NPC484816
0.5165	Remote Similarity	NPC469438
0.5119	Remote Similarity	NPC10205
0.5116	Remote Similarity	NPC478797
0.5116	Remote Similarity	NPC33298
0.5111	Remote Similarity	NPC11411
0.5111	Remote Similarity	NPC485745
0.5055	Remote Similarity	NPC133984

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC327032 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3839
0.1-0.2	5132
0.2-0.3	169
0.3-0.4	9
0.4-0.5	1
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