NPASS Compound

Structure

NPC39308 OpenBabel07101718282D 33 38 0 0 1 0 0 0 0 0999 V2000 -2.7557 3.4380 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6878 2.9233 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9856 -0.2606 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8439 -1.4616 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6878 -0.9744 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0738 -0.0061 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9283 0.4872 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.9744 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5317 1.4616 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3573 3.9706 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0177 2.3173 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8439 1.4616 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3755 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5738 2.6538 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8185 2.9201 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2342 1.0006 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8439 0.4872 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7102 3.2420 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6878 1.9489 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5317 0.4872 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.3118 3.7745 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.8812 1.7292 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.2194 0.4872 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.9283 1.4738 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6878 -0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.6193 2.8499 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.0738 1.9671 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.9722 2.1213 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8439 0.4872 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.2194 1.4738 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -5.2797 1.1966 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.6878 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3 31 1 0 0 0 0 4 5 1 0 0 0 0 4 8 1 0 0 0 0 6 7 1 0 0 0 0 6 23 1 0 0 0 0 8 32 1 0 0 0 0 9 19 1 0 0 0 0 9 20 1 0 0 0 0 10 18 1 0 0 0 0 11 18 1 0 0 0 0 12 19 1 0 0 0 0 15 21 1 0 0 0 0 16 22 1 0 0 0 0 16 31 1 0 0 0 0 17 32 1 0 0 0 0 17 33 2 0 0 0 0 18 1 1 1 0 0 0 19 2 1 1 0 0 0 20 13 1 1 0 0 0 20 25 1 0 0 0 0 21 10 1 6 0 0 0 21 26 1 0 0 0 0 22 14 1 6 0 0 0 22 24 1 0 0 0 0 23 13 1 6 0 0 0 23 30 1 0 0 0 0 24 7 1 6 0 0 0 24 27 1 0 0 0 0 25 5 1 6 0 0 0 25 29 1 0 0 0 0 26 14 1 6 0 0 0 26 28 1 0 0 0 0 27 15 1 1 0 0 0 27 30 1 0 0 0 0 28 11 1 1 0 0 0 28 31 1 0 0 0 0 29 12 1 1 0 0 0 29 32 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	455.39
Volume:	497.945
LogP:	4.68
LogD:	5.837
LogS:	-5.662
# Rotatable Bonds:	3
TPSA:	35.58
# H-Bond Aceptor:	4
# H-Bond Donor:	1
# Rings:	6
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.622
Synthetic Accessibility Score:	6.158
Fsp3:	0.966
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.968
MDCK Permeability:	7.585844286950305e-06
Pgp-inhibitor:	0.001
Pgp-substrate:	0.97
Human Intestinal Absorption (HIA):	0.019
20% Bioavailability (F20%):	0.004
30% Bioavailability (F30%):	0.902

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002
Plasma Protein Binding (PPB):	76.32223510742188%
Volume Distribution (VD):	0.791
Pgp-substrate:	5.359267711639404%

ADMET: Metabolism

CYP1A2-inhibitor:	0.02
CYP1A2-substrate:	0.134
CYP2C19-inhibitor:	0.122
CYP2C19-substrate:	0.927
CYP2C9-inhibitor:	0.114
CYP2C9-substrate:	0.079
CYP2D6-inhibitor:	0.816
CYP2D6-substrate:	0.873
CYP3A4-inhibitor:	0.421
CYP3A4-substrate:	0.858

ADMET: Excretion

Clearance (CL):	4.193
Half-life (T1/2):	0.378

ADMET: Toxicity

hERG Blockers:	0.977
Human Hepatotoxicity (H-HT):	0.991
Drug-inuced Liver Injury (DILI):	0.97
AMES Toxicity:	0.006
Rat Oral Acute Toxicity:	0.017
Maximum Recommended Daily Dose:	0.479
Skin Sensitization:	0.971
Carcinogencity:	0.013
Eye Corrosion:	0.054
Eye Irritation:	0.025
Respiratory Toxicity:	0.732

Download Data

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

Natural Product: NPC39308

Natural Product ID:	NPC39308
*Common Name:**	Serratezomine D
IUPAC Name:	n.a.
Synonyms:	Serratezomine D
Standard InCHIKey:	GLLIOBCNWZQYCM-JTDWSUOPSA-N
Standard InCHI:	InChI=1S/C29H49N3O/c1-18-10-21-15-27-24(22-14-26(21)28(11-18)31(3)16-22)7-6-23(30-27)13-20-9-19(2)12-29-25(20)5-4-8-32(29)17-33/h17-30H,4-16H2,1-3H3/t18-,19-,20-,21-,22+,23+,24-,25-,26-,27-,28-,29-/m1/s1
SMILES:	O=CN1CCC[C@H]2[C@H]1C[C@H](C)C[C@@H]2C[C@@H]1CC[C@H]2[C@H](N1)C[C@H]1C[C@@H](C)C[C@@H]3[C@@H]1C[C@H]2CN3C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL507157
PubChem CID:	44511345
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0003787] Quinolidines

*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
NPO32462.1	Huperzia serrata	Under-species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[19447614]

☑ 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
Individual Protein	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT66	Individual Protein	Acetylcholinesterase	Electrophorus electricus	IC50	=	600000.0	nM	PMID[533591]

☑ 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 NPC39308 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	429
0.1-0.2	21619
0.2-0.3	14947
0.3-0.4	5184
0.4-0.5	405
0.5-0.6	81
0.6-0.7	29
0.7-0.8	2
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.7241	Intermediate Similarity	NPC57163
0.7241	Intermediate Similarity	NPC116881
0.7108	Intermediate Similarity	NPC25110
0.6667	Remote Similarity	NPC17770
0.6506	Remote Similarity	NPC473442
0.6506	Remote Similarity	NPC120167
0.65	Remote Similarity	NPC469970
0.6463	Remote Similarity	NPC271640
0.6375	Remote Similarity	NPC53276
0.6277	Remote Similarity	NPC43308
0.6196	Remote Similarity	NPC153734
0.6023	Remote Similarity	NPC477002
0.6	Remote Similarity	NPC243635
0.6	Remote Similarity	NPC151004
0.6	Remote Similarity	NPC271803
0.6	Remote Similarity	NPC68043
0.6	Remote Similarity	NPC180401
0.6	Remote Similarity	NPC206241
0.6	Remote Similarity	NPC266383
0.6	Remote Similarity	NPC48448
0.6	Remote Similarity	NPC290231
0.6	Remote Similarity	NPC228980
0.5875	Remote Similarity	NPC21781
0.587	Remote Similarity	NPC12035
0.5814	Remote Similarity	NPC124384
0.5806	Remote Similarity	NPC90150
0.5667	Remote Similarity	NPC80447
0.5663	Remote Similarity	NPC89921
0.5632	Remote Similarity	NPC245223
0.5612	Remote Similarity	NPC21035

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 NPC39308 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	178
0.1-0.2	3417
0.2-0.3	4641
0.3-0.4	802
0.4-0.5	79
0.5-0.6	26
0.6-0.7	6
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
0.6667	Remote Similarity	NPD3721	Approved
0.6667	Remote Similarity	NPD3722	Approved
0.6404	Remote Similarity	NPD3155	Clinical (unspecified phase)
0.6292	Remote Similarity	NPD7155	Clinical (unspecified phase)
0.6267	Remote Similarity	NPD3727	Discontinued
0.6	Remote Similarity	NPD1822	Approved
0.6	Remote Similarity	NPD1823	Approved
0.6	Remote Similarity	NPD1821	Approved
0.5758	Remote Similarity	NPD6934	Discontinued

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