NPASS Compound

Natural Product: NPC571406

Natural Product ID	NPC571406
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	methyl (3~{R})-3-[(10~{R},13~{R},17~{R})-10,13-dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl]butanoate
IUPAC Name	methyl (3~{R})-3-[(10~{R},13~{R},17~{R})-10,13-dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl]butanoate
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 63 66 0 0 0 0 0 0 0 0999 V2000 5.7197 2.5895 1.2980 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5498 1.5128 0.3925 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3068 1.3028 -0.2688 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4271 2.1325 0.0252 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1696 0.1632 -1.2116 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6036 -1.0743 -0.6382 C 0 0 1 0 0 0 0 0 0 0 0 0 4.4600 -1.5191 0.5243 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1816 -1.3315 -0.6172 C 0 0 1 0 0 0 0 0 0 0 0 0 1.9284 -2.6803 0.0718 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5067 -2.6001 0.5665 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0533 -1.4422 -0.1347 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2767 -0.8217 0.4475 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3127 -1.8936 0.6172 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4921 -1.2418 1.3390 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9687 -0.1410 0.4682 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2754 0.0258 0.3506 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8945 1.0638 -0.4688 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1314 1.2873 -0.4860 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0354 1.9267 -1.3484 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7620 1.1375 -1.5673 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0762 0.7704 -0.2677 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9380 2.0358 0.5491 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7560 0.1660 -0.6170 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6538 1.2094 -0.7605 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6447 0.5780 -1.1440 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1449 -0.4533 -0.1351 C 0 0 2 0 0 0 0 0 0 0 0 0 1.2137 0.0566 1.2515 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7630 3.0102 1.2186 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0203 3.4233 1.0560 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5992 2.2707 2.3459 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6060 0.5668 -2.0811 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2091 0.0183 -1.6391 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9679 -1.8796 -1.4358 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5487 -2.6089 0.6336 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5163 -1.1837 0.2805 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2183 -0.9756 1.4585 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8748 -1.5834 -1.7041 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0894 -3.5318 -0.6016 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5645 -2.8016 0.9727 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0453 -3.5225 0.2177 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4180 -2.6086 1.6655 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2453 -1.6756 -1.1904 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1579 -0.3287 1.4175 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6816 -2.2992 -0.3340 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8656 -2.6860 1.2799 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2390 -2.0278 1.4824 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1958 -0.8728 2.3440 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9560 -0.6476 0.8938 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5597 1.9709 -2.3233 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8348 2.9044 -0.9007 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0645 1.6764 -2.2486 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0190 0.1883 -2.0803 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9254 2.3508 0.9163 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2970 1.8828 1.4481 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5386 2.8871 -0.0620 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7761 -0.3965 -1.5724 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6215 1.9333 0.0502 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9695 1.8074 -1.6694 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3984 -0.0500 -2.0607 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3636 1.3624 -1.3869 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7569 -0.6294 2.0079 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6323 0.9977 1.3278 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2156 0.2998 1.6422 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 3 5 1 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 1 0 15 16 2 0 16 17 1 0 17 18 2 0 17 19 1 0 19 20 1 0 20 21 1 0 21 22 1 1 21 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 1 26 8 1 0 26 11 1 0 23 12 1 0 21 15 1 0 1 28 1 0 1 29 1 0 1 30 1 0 5 31 1 0 5 32 1 0 6 33 1 6 7 34 1 0 7 35 1 0 7 36 1 0 8 37 1 6 9 38 1 0 9 39 1 0 10 40 1 0 10 41 1 0 11 42 1 0 12 43 1 0 13 44 1 0 13 45 1 0 14 46 1 0 14 47 1 0 16 48 1 0 19 49 1 0 19 50 1 0 20 51 1 0 20 52 1 0 22 53 1 0 22 54 1 0 22 55 1 0 23 56 1 0 24 57 1 0 24 58 1 0 25 59 1 0 25 60 1 0 27 61 1 0 27 62 1 0 27 63 1 0 M END

Standard InCHIKey	JEGXOFSOVHNFEU-WFVYKGBRSA-N
Standard InCHI	InChI=1S/C24H36O3/c1-15(13-22(26)27-4)19-7-8-20-18-6-5-16-14-17(25)9-11-23(16,2)21(18)10-12-24(19,20)3/h14-15,18-21H,5-13H2,1-4H3/t15-,18?,19-,20?,21?,23+,24-/m1/s1
SMILES	COC(=O)C[C@@H](C)[C@H]1CCC2C3CCC4=CC(=O)CC[C@]4(C)C3CC[C@@]21C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	372.27	Volume:	407.896 ? Van der Waals volume.
Dense:	0.913	LogP:	4.244 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.677 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.79 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	22.0
TPSA:	43.37 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	0.0	Rings:	4.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.629	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.095	Fsp³:	0.833
MCE-18:	68.545 ? 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:	0.587	Fluc inhibitor:	0.006 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.007 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.002 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.508	Promiscuous compounds:	0.194

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.733	MDCK Permeability:	-4.915
Pgp-inhibitor:	0.831	Pgp-substrate:	0.001
PAMPA:	0.032 ? 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%):	0.151	30% Bioavailability (F30%):	0.359
50% Bioavailability (F50%):	0.872

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.162	MRP1:	0.88
Plasma Protein Binding (PPB):	97.761%	Volume Distribution (VD):	-0.317
Fu:	2.54% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.994
OATP1B3 inhibitor:	0.984	BCRP inhibitor:	0.02
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.972	CYP1A2-substrate:	0.842
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.208
CYP2C9-inhibitor:	0.969	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.034	CYP2D6-substrate:	0.071
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.987
CYP2B6-substrate:	0.997	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

14.417

Half-life (T1/2):

0.705

ADMET: Toxicity

hERG Blockers:	0.156	hERG Blockers (10um):	0.601
Human Hepatotoxicity (H-HT):	0.732	Drug-induced Liver Injury (DILI):	0.201
AMES Toxicity:	0.164	Rat Oral Acute Toxicity:	0.271
Maximum Recommended Daily Dose:	0.441	Skin Sensitization:	0.8
Carcinogencity:	0.827	Eye Corrosion:	0.104
Eye Irritation:	0.601	Respiratory Toxicity:	0.47
Drug-induced Neurotoxicity:	0.663	Ototoxicity:	0.614
Hematotoxicity:	0.302	Drug-induced Nephrotoxicity:	0.344
Genotoxicity:	0.063	RPMI-8226 Immunitoxicity:	0.052
A549 Cytotoxicity:	0.048	Hek293 Cytotoxicity:	0.186
BCF:	1.235 ? 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:	4.264 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.715 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.035 ? 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
NPO5007	Deltocyathus magnificus	Species	Caryophylliidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5007	Deltocyathus magnificus	Species	Caryophylliidae	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 NPC571406 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	19040
0.1-0.2	26626
0.2-0.3	3949
0.3-0.4	174
0.4-0.5	35
0.5-0.6	21
0.6-0.7	5
0.7-0.8	1
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
0.76	Intermediate Similarity	NPC282593
0.7451	Intermediate Similarity	NPC35734
0.7451	Intermediate Similarity	NPC159577
0.7451	Intermediate Similarity	NPC602429
0.7308	Intermediate Similarity	NPC149203
0.7115	Intermediate Similarity	NPC115023
0.7	Intermediate Similarity	NPC307176
0.7	Intermediate Similarity	NPC321874
0.6604	Remote Similarity	NPC214043
0.6604	Remote Similarity	NPC85774
0.6552	Remote Similarity	NPC320514
0.6545	Remote Similarity	NPC249312
0.6364	Remote Similarity	NPC237712
0.5849	Remote Similarity	NPC139397
0.5714	Remote Similarity	NPC227064
0.5714	Remote Similarity	NPC329043
0.5714	Remote Similarity	NPC58841
0.5714	Remote Similarity	NPC161423
0.569	Remote Similarity	NPC303613
0.569	Remote Similarity	NPC323765
0.5636	Remote Similarity	NPC2634
0.5636	Remote Similarity	NPC265782
0.5636	Remote Similarity	NPC251929
0.55	Remote Similarity	NPC469948
0.5345	Remote Similarity	NPC144258
0.5345	Remote Similarity	NPC327115
0.5323	Remote Similarity	NPC309603
0.5172	Remote Similarity	NPC255021
0.5172	Remote Similarity	NPC474228
0.5156	Remote Similarity	NPC305039
0.5156	Remote Similarity	NPC205860
0.5082	Remote Similarity	NPC310010
0.5082	Remote Similarity	NPC326627
0.5075	Remote Similarity	NPC187159

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC571406 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6386
0.1-0.2	2489
0.2-0.3	188
0.3-0.4	59
0.4-0.5	9
0.5-0.6	16
0.6-0.7	2
0.7-0.8	1
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
0.7	Intermediate Similarity	NPD4747	Phase 4
0.6316	Remote Similarity	NPD5737	Phase 4
0.6102	Remote Similarity	NPD6672	Phase 4
0.5714	Remote Similarity	NPD3666	Phase 4
0.5667	Remote Similarity	NPD6409	Approved
0.5636	Remote Similarity	NPD4691	Approved
0.5593	Remote Similarity	NPD5330	Phase 4
0.5593	Remote Similarity	NPD6938	Clinical (unspecified phase)
0.5593	Remote Similarity	NPD6939	Phase 3
0.5439	Remote Similarity	NPD4221	Phase 4
0.5167	Remote Similarity	NPD4693	Phase 3
0.5156	Remote Similarity	NPD6083	Phase 4
0.5156	Remote Similarity	NPD6084	Phase 2
0.5156	Remote Similarity	NPD6684	Phase 4
0.5156	Remote Similarity	NPD6904	Phase 4
0.5156	Remote Similarity	NPD7334	Approved
0.5156	Remote Similarity	NPD7521	Phase 4
0.5082	Remote Similarity	NPD4753	Phase 2
0.5077	Remote Similarity	NPD6903	Phase 4

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