NPASS Compound

Natural Product: NPC540868

Natural Product ID	NPC540868
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	TANAKINE
IUPAC Name	1-(1~{H}-indol-3-yl)-3-methyl-butane-2,3-diol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
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 33 34 0 0 0 0 0 0 0 0999 V2000 -3.0006 -0.7271 -0.0915 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0967 0.3858 0.3690 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9472 1.4369 1.0583 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2123 -0.1101 1.3086 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3492 1.0493 -0.7946 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5884 2.1087 -0.3486 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5544 -0.0038 -1.5162 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4509 -0.6879 -0.6778 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3148 -1.9403 -0.0843 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4178 -2.2305 0.6158 N 0 0 0 0 0 0 0 0 0 0 0 0 2.2908 -1.2251 0.5174 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5523 -1.0281 1.0327 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1973 0.1513 0.7225 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6516 1.1210 -0.0617 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3838 0.9204 -0.5779 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6984 -0.2475 -0.2927 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7174 -1.7075 0.3753 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0425 -0.8307 -1.1950 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0611 -0.5215 0.2102 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9424 1.0124 1.2599 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5267 1.7291 2.0451 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0744 2.3410 0.4448 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5875 -0.8639 1.8207 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1484 1.4708 -1.4368 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1902 1.9794 0.5356 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0450 0.5507 -2.3679 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2124 -0.7211 -2.0351 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5609 -2.5579 -0.1945 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6217 -3.1021 1.1774 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0143 -1.7898 1.6648 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1842 0.3135 1.1214 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1598 2.0554 -0.3092 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9201 1.6691 -1.2145 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 2 5 1 0 5 6 1 0 5 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 8 1 0 16 11 1 0 1 17 1 0 1 18 1 0 1 19 1 0 3 20 1 0 3 21 1 0 3 22 1 0 4 23 1 0 5 24 1 0 6 25 1 0 7 26 1 0 7 27 1 0 9 28 1 0 10 29 1 0 12 30 1 0 13 31 1 0 14 32 1 0 15 33 1 0 M END

Standard InCHIKey	JPRWHAIHJJJQTF-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C13H17NO2/c1-13(2,16)12(15)7-9-8-14-11-6-4-3-5-10(9)11/h3-6,8,12,14-16H,7H2,1-2H3
SMILES	CC(C)(O)C(O)CC1=CNC2=CC=CC=C12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	219.13	Volume:	234.323 ? Van der Waals volume.
Dense:	0.935	LogP:	2.01 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.091 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.706 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	10.0
TPSA:	56.25 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	3.0	Rings:	2.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.737	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.632	Fsp³:	0.385
MCE-18:	26.0 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.071	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.046 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.017 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.152	Promiscuous compounds:	0.234

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.581	MDCK Permeability:	-4.519
Pgp-inhibitor:	0.001	Pgp-substrate:	0.465
PAMPA:	0.587 ? 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):	0.003
20% Bioavailability (F20%):	0.015	30% Bioavailability (F30%):	0.142
50% Bioavailability (F50%):	0.861

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.888	MRP1:	0.584
Plasma Protein Binding (PPB):	69.213%	Volume Distribution (VD):	-0.067
Fu:	31.184% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.802
OATP1B3 inhibitor:	0.963	BCRP inhibitor:	0.496
BSEP inhibitor:	0.188

ADMET: Metabolism

CYP1A2-inhibitor:	0.012	CYP1A2-substrate:	0.38
CYP2C19-inhibitor:	0.009	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.313	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.899	CYP2D6-substrate:	0.34
CYP3A4-inhibitor:	0.07	CYP3A4-substrate:	0.004
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.965
HLM stability:	0.444 ? 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):

10.48

Half-life (T1/2):

1.435

ADMET: Toxicity

hERG Blockers:	0.109	hERG Blockers (10um):	0.566
Human Hepatotoxicity (H-HT):	0.485	Drug-induced Liver Injury (DILI):	0.058
AMES Toxicity:	0.524	Rat Oral Acute Toxicity:	0.212
Maximum Recommended Daily Dose:	0.548	Skin Sensitization:	0.319
Carcinogencity:	0.496	Eye Corrosion:	0.007
Eye Irritation:	0.803	Respiratory Toxicity:	0.547
Drug-induced Neurotoxicity:	0.435	Ototoxicity:	0.663
Hematotoxicity:	0.155	Drug-induced Nephrotoxicity:	0.27
Genotoxicity:	0.335	RPMI-8226 Immunitoxicity:	0.032
A549 Cytotoxicity:	0.049	Hek293 Cytotoxicity:	0.143
BCF:	0.312 ? 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:	2.824 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.28 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.338 ? 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
NPO2715	Murraya paniculata	Species	Rutaceae	Eukaryota	n.a.	leaf	n.a.	PMID[24354205]
NPO2715	Murraya paniculata	Species	Rutaceae	Eukaryota	n.a.	twig	n.a.	PMID[24354205]
NPO2715	Murraya paniculata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[34964904]
NPO2715	Murraya paniculata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36529712]
NPO2715	Murraya paniculata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2715	Murraya paniculata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO2715	Murraya paniculata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2715	Murraya paniculata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO2715	Murraya paniculata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO2715	Murraya paniculata	Species	Rutaceae	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 NPC540868 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	34049
0.1-0.2	14395
0.2-0.3	972
0.3-0.4	305
0.4-0.5	98
0.5-0.6	23
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
0.6809	Remote Similarity	NPC480551
0.6667	Remote Similarity	NPC230869
0.65	Remote Similarity	NPC601214
0.64	Remote Similarity	NPC480550
0.6136	Remote Similarity	NPC29886
0.6047	Remote Similarity	NPC96102
0.5909	Remote Similarity	NPC279081
0.5882	Remote Similarity	NPC469358
0.5714	Remote Similarity	NPC315555
0.5652	Remote Similarity	NPC84911
0.5581	Remote Similarity	NPC102423
0.5532	Remote Similarity	NPC73767
0.5417	Remote Similarity	NPC310665
0.5417	Remote Similarity	NPC605863
0.5345	Remote Similarity	NPC603162
0.5294	Remote Similarity	NPC190296
0.5283	Remote Similarity	NPC200214
0.5263	Remote Similarity	NPC606619
0.5263	Remote Similarity	NPC610347
0.5227	Remote Similarity	NPC53947
0.52	Remote Similarity	NPC267343
0.52	Remote Similarity	NPC78020
0.5192	Remote Similarity	NPC480318
0.5106	Remote Similarity	NPC72435
0.5098	Remote Similarity	NPC55772
0.5098	Remote Similarity	NPC59269
0.5098	Remote Similarity	NPC600736
0.5094	Remote Similarity	NPC609424
0.5085	Remote Similarity	NPC611171

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC540868 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6227
0.1-0.2	2750
0.2-0.3	130
0.3-0.4	35
0.4-0.5	3
0.5-0.6	3
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
0.6047	Remote Similarity	NPD198	Clinical (unspecified phase)
0.5745	Remote Similarity	NPD786	Pre-clinical
0.5283	Remote Similarity	NPD1722	Phase 4
0.5192	Remote Similarity	NPD749	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