NPASS Compound

Natural Product: NPC3715

Natural Product ID	NPC3715
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Ecliptalbine
IUPAC Name	2-[(1R)-1-[(3S,8S,9S,10R,13S,14S,17R)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethyl]-5-methylpyridin-3-ol
Synonyms	Ecliptalbine
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL457812
PubChem CID	10692897
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0003569] Pregnane steroids [CHEMONTID:0001468] Gluco/mineralocorticoids, progestogins and derivatives

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 69 73 0 0 0 0 0 0 0 0999 V2000 -7.3097 0.6154 2.2134 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2158 0.4086 1.2091 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4417 0.5830 -0.1443 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4147 0.3861 -1.0540 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1349 0.0105 -0.6452 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0621 -0.2203 -1.5815 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.8696 -1.7235 -1.8465 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7854 0.4404 -1.4918 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7820 1.9584 -1.5888 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3995 2.3841 -1.1162 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3081 1.0656 -0.9888 C 0 0 1 0 0 0 0 0 0 0 0 0 1.5471 1.0360 -0.2259 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6210 1.8257 -0.9455 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8192 1.8169 -0.0857 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1170 0.7409 0.6041 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3313 0.7592 1.4618 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2419 -0.3140 0.8866 C 0 0 2 0 0 0 0 0 0 0 0 0 5.6341 -1.0763 -0.2416 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2444 -1.5629 -0.0381 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3242 -0.5114 0.5893 C 0 0 1 0 0 0 0 0 0 0 0 0 3.1316 -0.9585 2.0224 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0280 -0.3997 -0.1531 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9779 -1.2510 0.5204 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3745 -1.1402 -0.1064 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8402 0.2389 -0.3690 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.2582 0.9921 0.8645 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8184 -1.1152 1.8710 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9907 -0.1393 0.6745 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.9452 0.0379 1.5886 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6980 0.5755 -2.4032 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.9202 0.8524 3.2025 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9263 -0.3281 2.2044 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9730 1.4170 1.8207 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4349 0.8729 -0.4429 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4781 0.1077 -2.6268 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8674 -2.0816 -2.2505 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1312 -1.8928 -2.6477 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7206 -2.3042 -0.9389 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1908 0.1316 -2.4280 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8919 2.2382 -2.6803 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6067 2.4505 -1.0869 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1043 2.9605 -1.9454 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4191 2.9899 -0.2105 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4592 0.6547 -1.9850 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5468 1.4047 0.8094 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2771 2.8486 -1.2006 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8757 1.2444 -1.8645 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4468 2.6855 -0.0224 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1068 0.6000 2.5382 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8157 1.7714 1.4324 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1199 0.2435 0.4390 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2782 -1.9896 -0.3896 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7602 -0.5051 -1.2047 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2182 -2.5128 0.5192 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8049 -1.7815 -1.0415 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6614 -0.1787 2.6550 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1417 -1.1731 2.4375 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5960 -1.9289 2.0881 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1586 -0.7856 -1.1799 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3050 -2.3050 0.4322 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9174 -0.9153 1.5959 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0692 -1.6466 0.6277 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3917 -1.7404 -1.0338 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3919 1.6031 1.2792 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4876 0.3112 1.7252 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0255 1.7685 0.6985 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5587 -1.6015 1.4413 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7623 -0.1010 2.6566 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0857 -0.2151 -2.9029 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 1 0 6 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 2 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 1 20 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 1 17 27 1 0 5 28 1 0 28 29 2 0 4 30 1 0 29 2 1 0 25 8 1 0 25 11 1 0 22 12 1 0 20 15 1 0 1 31 1 0 1 32 1 0 1 33 1 0 3 34 1 0 6 35 1 6 7 36 1 0 7 37 1 0 7 38 1 0 8 39 1 6 9 40 1 0 9 41 1 0 10 42 1 0 10 43 1 0 11 44 1 6 12 45 1 1 13 46 1 0 13 47 1 0 14 48 1 0 16 49 1 0 16 50 1 0 17 51 1 6 18 52 1 0 18 53 1 0 19 54 1 0 19 55 1 0 21 56 1 0 21 57 1 0 21 58 1 0 22 59 1 6 23 60 1 0 23 61 1 0 24 62 1 0 24 63 1 0 26 64 1 0 26 65 1 0 26 66 1 0 27 67 1 0 29 68 1 0 30 69 1 0 M END

Standard InCHIKey	RODDEOSIMRCKKR-QWMOJLDXSA-N
Standard InCHI	InChI=1S/C27H39NO2/c1-16-13-24(30)25(28-15-16)17(2)21-7-8-22-20-6-5-18-14-19(29)9-11-26(18,3)23(20)10-12-27(21,22)4/h5,13,15,17,19-23,29-30H,6-12,14H2,1-4H3/t17-,19+,20+,21-,22+,23+,26+,27-/m1/s1
SMILES	Cc1cc(c([C@H](C)[C@H]2CC[C@H]3[C@@H]4CC=C5C[C@H](CC[C@]5(C)[C@H]4CC[C@]23C)O)nc1)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	409.3	Volume:	450.797 ? Van der Waals volume.
Dense:	0.908	LogP:	5.465 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.308 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.41 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	26.0
TPSA:	53.35 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	5.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.577	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.533	Fsp³:	0.741
MCE-18:	112.787 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.62	Fluc inhibitor:	0.011 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.146 ? 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:	0.011	Promiscuous compounds:	0.019

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.0	MDCK Permeability:	-4.923
Pgp-inhibitor:	0.054	Pgp-substrate:	0.052
PAMPA:	0.033 ? 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):	0.0
20% Bioavailability (F20%):	0.015	30% Bioavailability (F30%):	0.115
50% Bioavailability (F50%):	0.957

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.301	MRP1:	0.387
Plasma Protein Binding (PPB):	83.834%	Volume Distribution (VD):	-0.176
Fu:	18.025% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.922
BSEP inhibitor:	0.706

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.223	CYP2D6-substrate:	0.038
CYP3A4-inhibitor:	0.998	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.769
HLM stability:	0.139 ? 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):

13.082

Half-life (T1/2):

0.979

ADMET: Toxicity

hERG Blockers:	0.155	hERG Blockers (10um):	0.306
Human Hepatotoxicity (H-HT):	0.64	Drug-induced Liver Injury (DILI):	0.245
AMES Toxicity:	0.153	Rat Oral Acute Toxicity:	0.161
Maximum Recommended Daily Dose:	0.875	Skin Sensitization:	0.951
Carcinogencity:	0.834	Eye Corrosion:	0.03
Eye Irritation:	0.963	Respiratory Toxicity:	0.885
Drug-induced Neurotoxicity:	0.046	Ototoxicity:	0.494
Hematotoxicity:	0.2	Drug-induced Nephrotoxicity:	0.478
Genotoxicity:	0.293	RPMI-8226 Immunitoxicity:	0.083
A549 Cytotoxicity:	0.476	Hek293 Cytotoxicity:	0.812
BCF:	1.857 ? 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:	4.121 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.317 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.856 ? 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
NPO33146	eclipta alba	Species	n.a.	Eukaryota	n.a.	suriname rainforest1	n.a.	PMID[9784152]
NPO15546	Herba ecliptae prostratae	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15546	Herba ecliptae prostratae	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCMID]

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
IC12	3
MIC	2
IC50	1

Activity Type	# Activity
Cell line	1
Organism	5

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
NPT726	Cell line	M109	Mus musculus	IC50	>	20.0	ug.mL-1	PMID[9784152]
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	IC12	=	0.04	ug ml-1	PMID[9784152]
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	IC12	=	0.7	ug ml-1	PMID[9784152]
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	IC12	=	0.4	ug ml-1	PMID[9784152]
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	MIC	=	20.0	ug.mL-1	PMID[9784152]
NPT20	Organism	Candida albicans	Candida albicans	MIC	=	20.0	ug.mL-1	PMID[9784152]

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 NPC3715 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	11590
0.1-0.2	36603
0.2-0.3	1506
0.3-0.4	103
0.4-0.5	41
0.5-0.6	12
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	Natural Product ID
0.5286	Remote Similarity	NPC600590
0.5211	Remote Similarity	NPC136188
0.5211	Remote Similarity	NPC28657
0.5143	Remote Similarity	NPC162742
0.5143	Remote Similarity	NPC304309
0.5143	Remote Similarity	NPC470228
0.5139	Remote Similarity	NPC230301
0.5135	Remote Similarity	NPC318495
0.507	Remote Similarity	NPC22105
0.507	Remote Similarity	NPC221758
0.507	Remote Similarity	NPC34019
0.507	Remote Similarity	NPC107059

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC3715 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4410
0.1-0.2	4650
0.2-0.3	81
0.3-0.4	2
0.4-0.5	4
0.5-0.6	3
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
0.5211	Remote Similarity	NPD6942	Phase 4
0.5139	Remote Similarity	NPD7339	Approved
0.507	Remote Similarity	NPD4786	Phase 1

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