NPASS Compound

Natural Product: NPC170432

Natural Product ID	NPC170432
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	6Beta-Hydroxyloganin
IUPAC Name	methyl (1S,4aS,5S,6R,7R,7aR)-5,6-dihydroxy-7-methyl-1-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1,4a,5,6,7,7a-hexahydrocyclopenta[c]pyran-4-carboxylate
Synonyms	6Beta-Hydroxyloganin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL492202
PubChem CID	158641
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0002049] Terpene glycosides [CHEMONTID:0004081] Iridoid O-glycosides

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 54 56 0 0 0 0 0 0 0 0999 V2000 -2.9808 -3.1407 0.7060 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0555 -2.3932 0.1770 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5987 -0.9468 0.1475 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4712 -0.8816 -0.6662 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8363 0.3439 -0.5722 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.6958 0.3189 -1.3384 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4553 0.6852 -0.6470 C 0 0 2 0 0 0 0 0 0 0 0 0 1.0576 1.8349 -1.1759 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3739 2.1047 -0.7627 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1454 1.1793 -0.2169 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7097 -0.2074 0.0100 C 0 0 2 0 0 0 0 0 0 0 0 0 1.3676 -0.5072 -0.6215 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7262 -1.5628 0.2567 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3909 -2.7673 -0.5972 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7684 -1.9085 1.3146 C 0 0 2 0 0 0 0 0 0 0 0 0 2.4790 -0.5541 1.4426 C 0 0 1 0 0 0 0 0 0 0 0 0 3.6159 -0.6512 2.2055 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6412 -2.8329 0.7361 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4997 1.5421 0.1842 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2947 0.7214 0.7094 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9954 2.8411 0.0041 O 0 0 0 0 0 0 0 0 0 0 0 0 6.3071 3.2104 0.3875 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7719 1.3760 -1.1807 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1024 1.3564 -0.4962 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.6752 -0.0140 -0.3096 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.6414 0.0552 0.7019 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0229 2.1083 -1.2215 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2331 2.6437 -1.1213 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7056 -2.7718 1.5883 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9558 -2.5444 0.7977 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1758 -2.7365 -0.8698 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2787 -0.6444 1.1702 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6289 0.6555 0.4717 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1678 0.9195 0.4009 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7853 3.0926 -0.8868 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4580 -0.9383 -0.3968 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5198 -0.9115 -1.6630 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1609 -1.2166 0.7861 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2671 -3.1919 -1.0936 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3000 -2.4077 -1.3879 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1644 -3.4905 0.0268 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3316 -2.2402 2.2544 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7203 0.1479 1.8893 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6098 -1.5601 2.6328 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5819 -2.6240 0.8772 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6187 2.5842 1.2437 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3464 4.2873 0.6632 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0293 3.0923 -0.4612 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9277 1.1222 -2.2476 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0167 1.8330 0.5023 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1555 -0.4079 -1.2396 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9917 0.9732 0.8251 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1396 1.7691 -2.1418 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5776 3.2552 -1.7969 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 2 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 13 15 1 0 15 16 1 0 16 17 1 0 15 18 1 0 10 19 1 0 19 20 2 0 19 21 1 0 21 22 1 0 5 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 24 27 1 0 23 28 1 0 25 3 1 0 12 7 1 0 16 11 1 0 1 29 1 0 2 30 1 0 2 31 1 0 3 32 1 1 5 33 1 1 7 34 1 1 9 35 1 0 11 36 1 6 12 37 1 6 13 38 1 1 14 39 1 0 14 40 1 0 14 41 1 0 15 42 1 1 16 43 1 1 17 44 1 0 18 45 1 0 22 46 1 0 22 47 1 0 22 48 1 0 23 49 1 6 24 50 1 1 25 51 1 6 26 52 1 0 27 53 1 0 28 54 1 0 M END

Standard InCHIKey	QDEYKGKBMCIYCT-AZPIFPLPSA-N
Standard InCHI	InChI=1S/C17H26O11/c1-5-8-9(12(21)10(5)19)6(15(24)25-2)4-26-16(8)28-17-14(23)13(22)11(20)7(3-18)27-17/h4-5,7-14,16-23H,3H2,1-2H3/t5-,7-,8-,9-,10-,11-,12+,13+,14-,16+,17+/m1/s1
SMILES	OC[C@H]1O[C@@H](O[C@@H]2OC=C([C@@H]3[C@H]2[C@@H](C)[C@H]([C@H]3O)O)C(=O)OC)[C@@H]([C@H]([C@@H]1O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	406.15	Volume:	368.338 ? Van der Waals volume.
Dense:	1.103	LogP:	-1.238 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.605 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-0.668 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	17.0
TPSA:	175.37 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	6.0	Rings:	3.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.26	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.818	Fsp³:	0.824
MCE-18:	59.613 ? 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:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.419	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.158 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.25	Promiscuous compounds:	0.201

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.053	MDCK Permeability:	-5.152
Pgp-inhibitor:	0.0	Pgp-substrate:	0.389
PAMPA:	0.999 ? 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):	0.67
20% Bioavailability (F20%):	0.157	30% Bioavailability (F30%):	0.944
50% Bioavailability (F50%):	0.887

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.004	MRP1:	0.684
Plasma Protein Binding (PPB):	40.011%	Volume Distribution (VD):	-0.486
Fu:	57.563% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.993
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.007
BSEP inhibitor:	0.002

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.193
HLM stability:	0.003 ? 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):

0.994

Half-life (T1/2):

3.635

ADMET: Toxicity

hERG Blockers:	0.012	hERG Blockers (10um):	0.075
Human Hepatotoxicity (H-HT):	0.534	Drug-induced Liver Injury (DILI):	0.688
AMES Toxicity:	0.817	Rat Oral Acute Toxicity:	0.012
Maximum Recommended Daily Dose:	0.007	Skin Sensitization:	0.994
Carcinogencity:	0.155	Eye Corrosion:	0.0
Eye Irritation:	0.157	Respiratory Toxicity:	0.003
Drug-induced Neurotoxicity:	0.007	Ototoxicity:	0.984
Hematotoxicity:	0.443	Drug-induced Nephrotoxicity:	0.785
Genotoxicity:	0.059	RPMI-8226 Immunitoxicity:	0.076
A549 Cytotoxicity:	0.078	Hek293 Cytotoxicity:	0.064
BCF:	0.131 ? 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:	2.27 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.978 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.059 ? 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
NPO33172	nyctanthes arbortristis	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[1791475]
NPO33172	nyctanthes arbortristis	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22608855]

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	3
Survival	1

Activity Type	# Activity
Organism	4

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
NPT633	Organism	Leishmania donovani	Leishmania donovani	Inhibition	=	42.22	%	PubChem BioAssay data set
NPT633	Organism	Leishmania donovani	Leishmania donovani	Inhibition	=	65.77	%	PubChem BioAssay data set
NPT633	Organism	Leishmania donovani	Leishmania donovani	Inhibition	=	30.81	%	PMID[17500572]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT633	Organism	Leishmania donovani	Leishmania donovani	Survival	<	28.0	day	PMID[24224862]

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 NPC170432 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	20190
0.1-0.2	25964
0.2-0.3	3154
0.3-0.4	405
0.4-0.5	83
0.5-0.6	39
0.6-0.7	19
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
0.7414	Intermediate Similarity	NPC475928
0.7119	Intermediate Similarity	NPC35185
0.7119	Intermediate Similarity	NPC4899
0.7119	Intermediate Similarity	NPC177013
0.6721	Remote Similarity	NPC148270
0.6667	Remote Similarity	NPC474730
0.6613	Remote Similarity	NPC27687
0.6613	Remote Similarity	NPC106668
0.6557	Remote Similarity	NPC298255
0.6129	Remote Similarity	NPC117596
0.6094	Remote Similarity	NPC37240
0.6061	Remote Similarity	NPC254538
0.6032	Remote Similarity	NPC195510
0.6032	Remote Similarity	NPC255677
0.6032	Remote Similarity	NPC22149
0.6032	Remote Similarity	NPC13171
0.6032	Remote Similarity	NPC306344
0.6	Remote Similarity	NPC231710
0.6	Remote Similarity	NPC470573
0.6	Remote Similarity	NPC120021
0.6	Remote Similarity	NPC216826
0.6	Remote Similarity	NPC270908
0.6	Remote Similarity	NPC65665
0.5909	Remote Similarity	NPC475851
0.5909	Remote Similarity	NPC475924
0.5846	Remote Similarity	NPC61201
0.5821	Remote Similarity	NPC488472
0.5821	Remote Similarity	NPC257424
0.5758	Remote Similarity	NPC193741
0.5694	Remote Similarity	NPC488470
0.5672	Remote Similarity	NPC609500
0.5625	Remote Similarity	NPC303451
0.5625	Remote Similarity	NPC72358
0.5588	Remote Similarity	NPC222062
0.5538	Remote Similarity	NPC307699
0.5513	Remote Similarity	NPC475379
0.5513	Remote Similarity	NPC96599
0.5507	Remote Similarity	NPC41681
0.5455	Remote Similarity	NPC488467
0.5373	Remote Similarity	NPC110701
0.5342	Remote Similarity	NPC488456
0.5342	Remote Similarity	NPC488471
0.5342	Remote Similarity	NPC488466
0.5342	Remote Similarity	NPC488465
0.5342	Remote Similarity	NPC488460
0.5342	Remote Similarity	NPC488462
0.5316	Remote Similarity	NPC488468
0.5312	Remote Similarity	NPC63897
0.5303	Remote Similarity	NPC250545
0.5278	Remote Similarity	NPC197541
0.5278	Remote Similarity	NPC234304
0.5278	Remote Similarity	NPC118761
0.5278	Remote Similarity	NPC605627
0.525	Remote Similarity	NPC475484
0.5217	Remote Similarity	NPC6414
0.5217	Remote Similarity	NPC610085
0.52	Remote Similarity	NPC488457
0.52	Remote Similarity	NPC488464
0.52	Remote Similarity	NPC488463
0.5075	Remote Similarity	NPC170204
0.507	Remote Similarity	NPC310804
0.507	Remote Similarity	NPC261117

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC170432 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7166
0.1-0.2	1904
0.2-0.3	61
0.3-0.4	19
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