NPASS Compound

Structure

NPC34811 OpenBabel07101718182D 33 37 0 0 1 0 0 0 0 0999 V2000 -0.4483 1.6730 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6730 0.4483 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2399 -7.0247 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0198 -4.6133 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0872 -2.8625 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3292 -5.3473 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8766 -4.4040 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6037 -5.0532 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8966 -4.3461 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1580 -6.8585 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2244 -6.5001 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7944 -3.5696 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6730 -1.4483 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5015 -4.2767 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3801 -2.1554 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7071 0.7071 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7859 -6.1336 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.5696 -4.7944 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 5.7873 -6.0813 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.2767 -5.5015 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.8284 -3.8284 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.1554 -3.3801 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7071 -1.7071 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.4483 -2.6730 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2426 -5.2426 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.1213 -3.1213 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 7.3305 -5.2950 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.0000 -1.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.4824 -2.9319 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7071 0.7071 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 17 1 0 0 0 0 2 17 1 0 0 0 0 6 30 1 0 0 0 0 7 30 1 0 0 0 0 8 9 1 0 0 0 0 9 24 1 0 0 0 0 10 11 1 0 0 0 0 10 21 1 0 0 0 0 11 22 1 0 0 0 0 12 14 1 0 0 0 0 12 23 1 0 0 0 0 13 15 1 0 0 0 0 14 28 1 0 0 0 0 15 29 1 0 0 0 0 16 20 1 0 0 0 0 16 31 1 0 0 0 0 18 3 1 1 0 0 0 18 21 1 0 0 0 0 18 30 1 0 0 0 0 19 8 1 6 0 0 0 19 22 1 0 0 0 0 19 23 1 0 0 0 0 20 17 1 1 0 0 0 20 27 1 0 0 0 0 21 28 1 1 0 0 0 22 28 1 1 0 0 0 23 29 1 1 0 0 0 24 26 1 0 0 0 0 24 29 1 1 0 0 0 25 13 1 1 0 0 0 25 26 1 0 0 0 0 25 31 1 0 0 0 0 26 32 2 0 0 0 0 27 31 1 0 0 0 0 27 33 2 0 0 0 0 28 4 1 1 0 0 0 29 5 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	456.37
Volume:	501.659
LogP:	5.169
LogD:	3.963
LogS:	-3.567
# Rotatable Bonds:	4
TPSA:	40.62
# H-Bond Aceptor:	4
# H-Bond Donor:	0
# Rings:	5
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.542
Synthetic Accessibility Score:	4.893
Fsp3:	0.931
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	1
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.791
MDCK Permeability:	1.0733331691881176e-05
Pgp-inhibitor:	0.993
Pgp-substrate:	0.005
Human Intestinal Absorption (HIA):	0.006
20% Bioavailability (F20%):	0.005
30% Bioavailability (F30%):	0.402

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.74
Plasma Protein Binding (PPB):	82.32550811767578%
Volume Distribution (VD):	1.615
Pgp-substrate:	9.573216438293457%

ADMET: Metabolism

CYP1A2-inhibitor:	0.024
CYP1A2-substrate:	0.275
CYP2C19-inhibitor:	0.046
CYP2C19-substrate:	0.966
CYP2C9-inhibitor:	0.147
CYP2C9-substrate:	0.073
CYP2D6-inhibitor:	0.022
CYP2D6-substrate:	0.885
CYP3A4-inhibitor:	0.698
CYP3A4-substrate:	0.884

ADMET: Excretion

Clearance (CL):	20.507
Half-life (T1/2):	0.035

ADMET: Toxicity

hERG Blockers:	0.593
Human Hepatotoxicity (H-HT):	0.358
Drug-inuced Liver Injury (DILI):	0.726
AMES Toxicity:	0.009
Rat Oral Acute Toxicity:	0.69
Maximum Recommended Daily Dose:	0.18
Skin Sensitization:	0.764
Carcinogencity:	0.463
Eye Corrosion:	0.011
Eye Irritation:	0.011
Respiratory Toxicity:	0.976

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC34811

Natural Product ID:	NPC34811
*Common Name:**	Pachystermine A
IUPAC Name:	(3R)-1-[(3S,5R,8S,9S,10R,13S,14S,17S)-17-[(1S)-1-(dimethylamino)ethyl]-10,13-dimethyl-4-oxo-1,2,3,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-yl]-3-propan-2-ylazetidin-2-one
Synonyms:	Pachystermine A
Standard InCHIKey:	MHFGHEARXPBTQH-RYPSFVHFSA-N
Standard InCHI:	InChI=1S/C29H48N2O2/c1-17(2)20-16-31(27(20)33)25-13-15-29(5)23-12-14-28(4)21(18(3)30(6)7)10-11-22(28)19(23)8-9-24(29)26(25)32/h17-25H,8-16H2,1-7H3/t18-,19-,20-,21+,22-,23-,24-,25-,28+,29+/m0/s1
SMILES:	CC(C)[C@@H]1CN([C@H]2CC[C@]3(C)[C@H]4CC[C@]5(C)[C@H](CC[C@H]5[C@@H]4CC[C@H]3C2=O)[C@H](C)N(C)C)C1=O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL2087207
PubChem CID:	22296920
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001194] Oxosteroids

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO13852	Pachysandra terminalis	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22804108]
NPO13852	Pachysandra terminalis	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO13852	Pachysandra terminalis	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13852	Pachysandra terminalis	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO13852	Pachysandra terminalis	Species	Buxaceae	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	NP ID	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
IC50	1

Activity Type	# Activity
Cell Line	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT82	Cell Line	MDA-MB-231	Homo sapiens	IC50	=	320.0	nM	PMID[518768]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC34811 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	257
0.1-0.2	12313
0.2-0.3	16670
0.3-0.4	9874
0.4-0.5	3076
0.5-0.6	439
0.6-0.7	54
0.7-0.8	10
0.8-0.85	3
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.8404	Intermediate Similarity	NPC470592
0.8228	Intermediate Similarity	NPC473442
0.8228	Intermediate Similarity	NPC120167
0.7917	Intermediate Similarity	NPC474001
0.7738	Intermediate Similarity	NPC25110
0.7604	Intermediate Similarity	NPC292819
0.747	Intermediate Similarity	NPC110615
0.7303	Intermediate Similarity	NPC90150
0.699	Remote Similarity	NPC470596
0.6989	Remote Similarity	NPC311769
0.6989	Remote Similarity	NPC147513
0.6989	Remote Similarity	NPC182106
0.6962	Remote Similarity	NPC21781
0.6848	Remote Similarity	NPC215474
0.6847	Remote Similarity	NPC474006
0.6842	Remote Similarity	NPC43308
0.6824	Remote Similarity	NPC245223
0.6804	Remote Similarity	NPC312637
0.6792	Remote Similarity	NPC470595
0.6771	Remote Similarity	NPC259252
0.6737	Remote Similarity	NPC157479
0.6667	Remote Similarity	NPC140685
0.6635	Remote Similarity	NPC58200
0.6628	Remote Similarity	NPC124384
0.6627	Remote Similarity	NPC53276
0.6582	Remote Similarity	NPC151464
0.6582	Remote Similarity	NPC143597
0.6548	Remote Similarity	NPC469970
0.6456	Remote Similarity	NPC184819
0.6408	Remote Similarity	NPC184033
0.6373	Remote Similarity	NPC174117
0.6364	Remote Similarity	NPC135005
0.6346	Remote Similarity	NPC220111
0.6337	Remote Similarity	NPC476752
0.6337	Remote Similarity	NPC476753
0.6329	Remote Similarity	NPC53245
0.6329	Remote Similarity	NPC288296
0.6322	Remote Similarity	NPC271640
0.6321	Remote Similarity	NPC152718
0.6321	Remote Similarity	NPC476755
0.6293	Remote Similarity	NPC470593
0.6293	Remote Similarity	NPC470594
0.6275	Remote Similarity	NPC476754
0.6263	Remote Similarity	NPC237535
0.625	Remote Similarity	NPC21667
0.6173	Remote Similarity	NPC474105
0.6168	Remote Similarity	NPC226509
0.6126	Remote Similarity	NPC473994
0.6055	Remote Similarity	NPC469958
0.6042	Remote Similarity	NPC257962
0.6036	Remote Similarity	NPC476918
0.6034	Remote Similarity	NPC473573
0.6	Remote Similarity	NPC230677
0.5965	Remote Similarity	NPC124358
0.5946	Remote Similarity	NPC244982
0.5946	Remote Similarity	NPC476756
0.5929	Remote Similarity	NPC63511
0.5909	Remote Similarity	NPC475239
0.5876	Remote Similarity	NPC109533
0.5856	Remote Similarity	NPC476926
0.5856	Remote Similarity	NPC476328
0.5818	Remote Similarity	NPC97336
0.5806	Remote Similarity	NPC476904
0.58	Remote Similarity	NPC152684
0.5798	Remote Similarity	NPC475340
0.5778	Remote Similarity	NPC473225
0.5766	Remote Similarity	NPC476921
0.5761	Remote Similarity	NPC21773
0.5752	Remote Similarity	NPC476276
0.5747	Remote Similarity	NPC477740
0.5739	Remote Similarity	NPC143173
0.573	Remote Similarity	NPC189917
0.573	Remote Similarity	NPC39462
0.573	Remote Similarity	NPC43300
0.573	Remote Similarity	NPC96812
0.573	Remote Similarity	NPC168824
0.573	Remote Similarity	NPC107704
0.5728	Remote Similarity	NPC249312
0.5714	Remote Similarity	NPC266383
0.5714	Remote Similarity	NPC477857
0.5714	Remote Similarity	NPC180401
0.5714	Remote Similarity	NPC474962
0.5714	Remote Similarity	NPC271803
0.5714	Remote Similarity	NPC68043
0.5714	Remote Similarity	NPC48448
0.5714	Remote Similarity	NPC290231
0.5714	Remote Similarity	NPC206241
0.5686	Remote Similarity	NPC21035
0.5684	Remote Similarity	NPC7214
0.5663	Remote Similarity	NPC307063
0.5652	Remote Similarity	NPC40574
0.5652	Remote Similarity	NPC108131
0.5647	Remote Similarity	NPC127798
0.5641	Remote Similarity	NPC28224
0.561	Remote Similarity	NPC472828

Chemically structural similarity: II. Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC34811 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	131
0.1-0.2	2367
0.2-0.3	4720
0.3-0.4	1496
0.4-0.5	345
0.5-0.6	82
0.6-0.7	7
0.7-0.8	1
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8095	Intermediate Similarity	NPD7155	Clinical (unspecified phase)
0.7527	Intermediate Similarity	NPD6934	Discontinued
0.6296	Remote Similarity	NPD6920	Discontinued
0.6237	Remote Similarity	NPD4777	Suspended
0.6237	Remote Similarity	NPD4776	Phase 2
0.6195	Remote Similarity	NPD8298	Phase 2
0.6182	Remote Similarity	NPD6415	Discontinued
0.6117	Remote Similarity	NPD5769	Clinical (unspecified phase)
0.5888	Remote Similarity	NPD3103	Approved
0.5888	Remote Similarity	NPD3104	Approved
0.5888	Remote Similarity	NPD3102	Approved
0.5888	Remote Similarity	NPD3101	Approved
0.5833	Remote Similarity	NPD8418	Phase 2
0.5778	Remote Similarity	NPD5360	Phase 3
0.5778	Remote Similarity	NPD5361	Clinical (unspecified phase)
0.5714	Remote Similarity	NPD8040	Discontinued
0.5714	Remote Similarity	NPD7333	Discontinued
0.5652	Remote Similarity	NPD4789	Approved
0.5612	Remote Similarity	NPD3155	Clinical (unspecified phase)

Bioactivity similarity: Similar Natural Products in NPASS

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