NPASS Compound

Natural Product: NPC137210

Natural Product ID	NPC137210
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	HHDWDLBSGSYIQQ-RHZWLWFHSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	70696679
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 55 57 0 0 0 0 0 0 0 0999 V2000 -0.3291 -2.2574 -0.4878 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3328 -1.1444 -0.5605 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.1859 -0.1421 0.5633 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5518 0.3586 0.8579 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.8117 1.7690 0.5758 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7991 2.6335 0.6383 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5705 2.0946 0.9719 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1715 0.9235 0.2714 C 0 0 1 0 0 0 0 0 0 0 0 0 1.1154 0.5651 0.6748 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0388 0.5258 -0.3392 C 0 0 1 0 0 0 0 0 0 0 0 0 3.2125 1.4543 -0.1035 C 0 0 1 0 0 0 0 0 0 0 0 0 4.2135 0.6891 0.7388 C 0 0 2 0 0 0 0 0 0 0 0 0 4.8915 -0.2954 -0.2190 C 0 0 1 0 0 0 0 0 0 0 0 0 3.7522 -0.8387 -1.0920 C 0 0 1 0 0 0 0 0 0 0 0 0 4.0613 -2.3304 -1.2653 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1401 -2.9676 -0.0396 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5410 -0.7628 -0.4374 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8422 0.3639 -0.9582 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5626 -0.1110 1.6885 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7880 1.7989 -1.3265 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1318 2.3035 0.2255 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2875 3.5436 -0.0080 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2422 1.5153 0.1331 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5001 2.0642 -0.2069 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5297 -0.5341 0.1279 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.6836 -1.7670 -0.1803 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5923 -2.5324 0.9635 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5703 -0.8588 0.9904 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4588 -0.5705 -1.8005 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8123 -3.2515 -0.5591 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2236 -2.2426 0.4775 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3740 -2.1917 -1.3444 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7627 -0.7372 1.4264 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7390 0.2240 1.9648 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9980 3.6778 0.4297 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1086 1.0840 -0.8333 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5921 0.7842 -1.3259 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9017 2.4040 0.3746 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9509 1.3741 1.2015 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3194 -1.0848 0.4159 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7600 -0.4086 -2.0961 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0665 -2.3686 -1.7603 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3629 -2.8201 -1.9453 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4562 -2.6454 0.6055 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1615 1.1458 -0.4069 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0507 -0.0303 2.5470 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1000 1.9207 -2.0379 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3881 2.9432 -0.9024 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9710 2.3887 0.7611 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0875 1.2553 -0.6902 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8808 -0.0971 -0.8328 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1242 -2.3284 -1.0118 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6789 -2.5582 1.3472 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3260 -0.6922 1.9483 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8529 -1.2355 -2.4199 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 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 14 17 1 0 13 18 1 0 12 19 1 0 11 20 1 0 5 21 1 0 21 22 2 0 21 23 1 0 23 24 1 0 4 25 1 0 25 26 1 0 26 27 1 0 25 28 1 0 2 29 1 6 26 2 1 0 8 3 1 0 17 10 1 0 1 30 1 0 1 31 1 0 1 32 1 0 3 33 1 1 4 34 1 1 6 35 1 0 8 36 1 6 10 37 1 6 11 38 1 1 12 39 1 1 13 40 1 1 14 41 1 6 15 42 1 0 15 43 1 0 16 44 1 0 18 45 1 0 19 46 1 0 20 47 1 0 24 48 1 0 24 49 1 0 24 50 1 0 25 51 1 6 26 52 1 6 27 53 1 0 28 54 1 0 29 55 1 0 M END

Standard InCHIKey	HHDWDLBSGSYIQQ-RHZWLWFHSA-N
Standard InCHI	InChI=1S/C17H26O12/c1-17(25)8-7(10(20)13(17)23)5(14(24)26-2)4-27-15(8)29-16-12(22)11(21)9(19)6(3-18)28-16/h4,6-13,15-16,18-23,25H,3H2,1-2H3/t6-,7-,8-,9-,10+,11+,12-,13+,15+,16+,17+/m1/s1
SMILES	C[C@@]1([C@@H]2[C@@H](C(=CO[C@H]2O[C@H]2[C@@H]([C@H]([C@@H]([C@@H](CO)O2)O)O)O)C(=O)OC)[C@@H]([C@@H]1O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	422.14	Volume:	377.129 ? Van der Waals volume.
Dense:	1.119	LogP:	-1.244 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.529 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-0.606 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	17.0
TPSA:	195.6 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	7.0	Rings:	3.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.217	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.96	Fsp³:	0.824
MCE-18:	65.032 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.353	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.056 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.261	Promiscuous compounds:	0.374

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.432	MDCK Permeability:	-5.137
Pgp-inhibitor:	0.0	Pgp-substrate:	0.836
PAMPA:	1.0 ? 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):	0.862
20% Bioavailability (F20%):	0.694	30% Bioavailability (F30%):	0.984
50% Bioavailability (F50%):	0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.005	MRP1:	0.955
Plasma Protein Binding (PPB):	34.75%	Volume Distribution (VD):	-0.516
Fu:	63.87% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.985
OATP1B3 inhibitor:	0.993	BCRP inhibitor:	0.01
BSEP inhibitor:	0.0

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:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.285
HLM stability:	0.013 ? 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):

1.003

Half-life (T1/2):

3.225

ADMET: Toxicity

hERG Blockers:	0.006	hERG Blockers (10um):	0.073
Human Hepatotoxicity (H-HT):	0.609	Drug-induced Liver Injury (DILI):	0.931
AMES Toxicity:	0.944	Rat Oral Acute Toxicity:	0.03
Maximum Recommended Daily Dose:	0.01	Skin Sensitization:	1.0
Carcinogencity:	0.181	Eye Corrosion:	0.0
Eye Irritation:	0.358	Respiratory Toxicity:	0.023
Drug-induced Neurotoxicity:	0.013	Ototoxicity:	0.978
Hematotoxicity:	0.78	Drug-induced Nephrotoxicity:	0.948
Genotoxicity:	0.457	RPMI-8226 Immunitoxicity:	0.112
A549 Cytotoxicity:	0.253	Hek293 Cytotoxicity:	0.1
BCF:	0.059 ? 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:	2.116 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.873 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.01 ? 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
NPO30658	Lamiophlomis rotata	n.a.	n.a.	n.a.	aerial parts	Jiangzi County, Tibet, China	2007-Sep	PMID[22664131]
NPO30658	Lamiophlomis rotata	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30658	Lamiophlomis rotata	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[HerDing]
NPO4203	Phlomoides rotata	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO30658	Lamiophlomis rotata	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO4203	Phlomoides rotata	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO4203	Phlomoides rotata	Species	Lamiaceae	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

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

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 NPC137210 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	15957
0.1-0.2	29669
0.2-0.3	3594
0.3-0.4	480
0.4-0.5	93
0.5-0.6	35
0.6-0.7	20
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
0.7458	Intermediate Similarity	NPC148270
0.7119	Intermediate Similarity	NPC170432
0.6774	Remote Similarity	NPC37240
0.6721	Remote Similarity	NPC195510
0.6721	Remote Similarity	NPC13171
0.6721	Remote Similarity	NPC475928
0.6452	Remote Similarity	NPC298255
0.6406	Remote Similarity	NPC470573
0.6406	Remote Similarity	NPC120021
0.6406	Remote Similarity	NPC216826
0.6406	Remote Similarity	NPC193741
0.619	Remote Similarity	NPC35185
0.619	Remote Similarity	NPC4899
0.619	Remote Similarity	NPC177013
0.6154	Remote Similarity	NPC231710
0.6154	Remote Similarity	NPC270908
0.6154	Remote Similarity	NPC65665
0.6032	Remote Similarity	NPC474730
0.6032	Remote Similarity	NPC117596
0.6	Remote Similarity	NPC27687
0.6	Remote Similarity	NPC110701
0.6	Remote Similarity	NPC106668
0.597	Remote Similarity	NPC488472
0.597	Remote Similarity	NPC257424
0.5938	Remote Similarity	NPC255677
0.5938	Remote Similarity	NPC22149
0.5938	Remote Similarity	NPC306344
0.5758	Remote Similarity	NPC61201
0.5735	Remote Similarity	NPC254538
0.5694	Remote Similarity	NPC488456
0.5694	Remote Similarity	NPC488465
0.5694	Remote Similarity	NPC488460
0.5694	Remote Similarity	NPC488462
0.5588	Remote Similarity	NPC475851
0.5588	Remote Similarity	NPC475924
0.5588	Remote Similarity	NPC609500
0.5541	Remote Similarity	NPC488457
0.5541	Remote Similarity	NPC488464
0.5541	Remote Similarity	NPC488463
0.5538	Remote Similarity	NPC303451
0.5538	Remote Similarity	NPC72358
0.5507	Remote Similarity	NPC222062
0.5479	Remote Similarity	NPC488471
0.5479	Remote Similarity	NPC488466
0.5455	Remote Similarity	NPC307699
0.5429	Remote Similarity	NPC41681
0.5405	Remote Similarity	NPC488470
0.5303	Remote Similarity	NPC304163
0.525	Remote Similarity	NPC475379
0.525	Remote Similarity	NPC96599
0.5224	Remote Similarity	NPC250545
0.5205	Remote Similarity	NPC197541
0.5205	Remote Similarity	NPC234304
0.5205	Remote Similarity	NPC118761
0.5205	Remote Similarity	NPC605627
0.5143	Remote Similarity	NPC6414
0.5143	Remote Similarity	NPC610085

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC137210 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6488
0.1-0.2	2574
0.2-0.3	70
0.3-0.4	18
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