NPASS Compound

Natural Product: NPC600989

Natural Product ID	NPC600989
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	PTHHVPMFZWYYDK-ZFORQUDYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2074958
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 51 54 0 0 0 0 0 0 0 0999 V2000 6.9053 -0.5731 1.6984 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6871 -0.4940 0.4639 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7819 -0.4720 -0.3876 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2970 -0.4236 -0.1086 C 0 0 1 0 0 0 0 0 0 0 0 0 4.3395 -0.4563 0.8670 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3015 0.4663 0.6781 C 0 0 1 0 0 0 0 0 0 0 0 0 2.3366 0.2769 1.6221 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0093 0.0832 1.3900 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4778 0.0571 0.1335 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8945 -0.1448 -0.0693 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7653 -0.3258 0.9979 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1836 -0.5323 0.7496 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0942 -0.7177 1.7561 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4533 -0.9136 1.4742 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2400 -1.0781 2.4391 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.8357 -0.9131 0.1665 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1736 -1.1054 -0.1230 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1026 -1.2941 0.8951 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.5276 -1.0992 -1.4579 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6213 -0.9139 -2.4755 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0273 -0.9151 -3.8243 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2981 -0.7266 -2.1263 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8802 -0.7223 -0.8057 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6193 -0.5428 -0.4963 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1888 -0.2923 2.2417 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1537 -0.0961 2.4696 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6466 -0.0786 3.7851 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0017 1.8328 0.8042 C 0 0 2 0 0 0 0 0 0 0 0 0 3.0705 2.8476 1.0024 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7668 2.0024 -0.4915 C 0 0 1 0 0 0 0 0 0 0 0 0 5.8002 2.9199 -0.3561 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1866 0.6989 -1.0813 C 0 0 2 0 0 0 0 0 0 0 0 0 4.3857 0.3292 -2.1861 O 0 0 0 0 0 0 0 0 0 0 0 0 8.7392 -0.6254 -0.0818 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1935 -1.3809 -0.7003 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9192 0.4493 -0.3455 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0551 0.1868 -0.7925 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3217 -0.1664 -1.0631 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7629 -0.7134 2.7846 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5318 -0.5209 1.3855 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5630 -1.2474 -1.6953 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3483 -0.8660 -4.5545 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5530 -0.5768 -2.9089 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8229 -0.4289 3.1267 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4365 -0.6389 4.0781 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6793 1.8268 1.6814 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3507 2.7992 0.2967 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0366 2.4701 -1.2134 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6490 2.5787 -0.6833 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2137 0.8487 -1.5272 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3882 -0.6782 -2.2196 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 2 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 14 16 1 0 16 17 2 0 17 18 1 0 17 19 1 0 19 20 2 0 20 21 1 0 20 22 1 0 22 23 2 0 23 24 1 0 11 25 1 0 25 26 2 0 26 27 1 0 6 28 1 0 28 29 1 0 28 30 1 0 30 31 1 0 30 32 1 0 32 33 1 0 32 4 1 0 26 8 1 0 24 12 1 0 23 16 1 0 3 34 1 0 4 35 1 6 6 36 1 6 9 37 1 0 10 38 1 0 13 39 1 0 18 40 1 0 19 41 1 0 21 42 1 0 22 43 1 0 25 44 1 0 27 45 1 0 28 46 1 1 29 47 1 0 30 48 1 6 31 49 1 0 32 50 1 6 33 51 1 0 M END

Standard InCHIKey	PTHHVPMFZWYYDK-ZFORQUDYSA-N
Standard InCHI	InChI=1S/C21H18O12/c22-8-4-10(24)15-11(25)6-13(31-14(15)5-8)7-1-2-12(9(23)3-7)32-21-18(28)16(26)17(27)19(33-21)20(29)30/h1-6,16-19,21-24,26-28H,(H,29,30)/t16-,17-,18+,19-,21+/m0/s1
SMILES	O=C(O)[C@H]1O[C@@H](Oc2ccc(-c3cc(=O)c4c(O)cc(O)cc4o3)cc2O)[C@H](O)[C@@H](O)[C@@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	462.08	Volume:	419.301 ? Van der Waals volume.
Dense:	1.102	LogP:	0.952 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.206 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.163 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	25.0
TPSA:	207.35 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	7.0	Rings:	4.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.27	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.006	Fsp³:	0.238
MCE-18:	91.385 ? 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:	1	PAINS Alert:	0
Colloidal aggregators:	0.484	Fluc inhibitor:	0.362 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.953 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.886 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.31	Promiscuous compounds:	0.447

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.593	MDCK Permeability:	-5.076
Pgp-inhibitor:	0.0	Pgp-substrate:	0.864
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):	0.009
20% Bioavailability (F20%):	0.115	30% Bioavailability (F30%):	0.754
50% Bioavailability (F50%):	0.958

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.899
Plasma Protein Binding (PPB):	85.447%	Volume Distribution (VD):	-0.115
Fu:	11.732% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.005
OATP1B3 inhibitor:	0.067	BCRP inhibitor:	0.089
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.278	CYP2C9-substrate:	0.103
CYP2D6-inhibitor:	0.01	CYP2D6-substrate:	0.012
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.022
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.965
HLM stability:	0.063 ? 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):

1.381

Half-life (T1/2):

3.449

ADMET: Toxicity

hERG Blockers:	0.007	hERG Blockers (10um):	0.062
Human Hepatotoxicity (H-HT):	0.324	Drug-induced Liver Injury (DILI):	0.918
AMES Toxicity:	0.606	Rat Oral Acute Toxicity:	0.119
Maximum Recommended Daily Dose:	0.243	Skin Sensitization:	0.96
Carcinogencity:	0.057	Eye Corrosion:	0.001
Eye Irritation:	0.965	Respiratory Toxicity:	0.156
Drug-induced Neurotoxicity:	0.001	Ototoxicity:	0.353
Hematotoxicity:	0.039	Drug-induced Nephrotoxicity:	0.25
Genotoxicity:	0.921	RPMI-8226 Immunitoxicity:	0.131
A549 Cytotoxicity:	0.176	Hek293 Cytotoxicity:	0.323
BCF:	0.26 ? 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:	2.876 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.254 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.414 ? 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
NPO24456	Salvia lavandulifolia	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36986494]
NPO24456	Salvia lavandulifolia	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24456	Salvia lavandulifolia	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

Activity Type	# Activity
Activity	1

Activity Type	# Activity
Individual protein	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1422	Individual protein	ATP-binding cassette sub-family G member 2	Homo sapiens	Activity	n.a.	n.a.	n.a.	PMID[15205350]

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 NPC600989 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	21408
0.1-0.2	25951
0.2-0.3	1666
0.3-0.4	610
0.4-0.5	189
0.5-0.6	17
0.6-0.7	13
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
0.6867	Remote Similarity	NPC191306
0.6667	Remote Similarity	NPC235260
0.6667	Remote Similarity	NPC135277
0.6667	Remote Similarity	NPC155763
0.6667	Remote Similarity	NPC20505
0.6588	Remote Similarity	NPC608742
0.6548	Remote Similarity	NPC138927
0.6471	Remote Similarity	NPC282169
0.6471	Remote Similarity	NPC210094
0.6395	Remote Similarity	NPC43211
0.6353	Remote Similarity	NPC101191
0.6279	Remote Similarity	NPC237435
0.6133	Remote Similarity	NPC52005
0.5843	Remote Similarity	NPC115760
0.573	Remote Similarity	NPC49344
0.5667	Remote Similarity	NPC601710
0.5652	Remote Similarity	NPC4390
0.5632	Remote Similarity	NPC143851
0.5444	Remote Similarity	NPC21100
0.5385	Remote Similarity	NPC60735
0.5385	Remote Similarity	NPC26230
0.5326	Remote Similarity	NPC609478
0.5294	Remote Similarity	NPC253685
0.5281	Remote Similarity	NPC254306
0.5269	Remote Similarity	NPC88023
0.5269	Remote Similarity	NPC309025
0.5128	Remote Similarity	NPC231772
0.5128	Remote Similarity	NPC601901
0.5104	Remote Similarity	NPC107987
0.5054	Remote Similarity	NPC219904

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC600989 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4098
0.1-0.2	4974
0.2-0.3	68
0.3-0.4	7
0.4-0.5	1
0.5-0.6	0
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	Drug ID	Developmental Stage
0.6279	Remote Similarity	NPD4338	Clinical (unspecified phase)

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