NPASS Compound

Structure

NPC469444 OpenBabel07101719512D 66 68 0 0 1 0 0 0 0 0999 V2000 9.6000 -1.7982 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4295 7.8870 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.0768 0.0849 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6644 6.3876 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5795 -1.2938 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.6722 4.6087 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 0.9712 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.9038 -1.1209 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0889 6.9774 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8845 3.1521 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4157 2.3391 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.0801 5.9811 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0133 4.1956 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.3700 6.9081 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8569 4.0719 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9147 3.0986 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 11.6856 5.4789 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.1580 3.4127 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4568 0.8411 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1422 -0.1794 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 7.7064 6.2277 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 5.7657 -0.3405 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 10.7378 5.2666 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 11.9755 6.4059 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3854 2.3926 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.5840 4.9324 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 9.2103 3.2003 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 11.3177 7.1204 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4281 0.8411 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 6.4797 4.6543 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 8.4461 0.4978 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.8561 -0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 7.3658 5.3181 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.4923 3.3579 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2638 2.2305 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3993 -0.8411 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1064 0.6174 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4506 5.3709 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2069 4.8325 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6635 -0.0774 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5862 3.8582 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 12.9232 6.6183 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 -1.0248 2.9916 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.1175 4.6713 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.3835 3.9117 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.5978 1.4448 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.9068 4.2362 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 8.9995 1.2959 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 4.3705 -0.8411 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 8.8448 4.1001 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 6.4126 5.5043 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 11.6076 8.0474 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9137 1.6822 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3852 4.3030 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5577 3.6222 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 10.2291 2.1237 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9137 -1.6822 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3740 -0.0204 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1607 6.2979 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 8.8244 5.5822 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 8.1021 -0.9440 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9712 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -0.9712 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9712 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7366 -0.3673 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 1 8 1 0 0 0 0 2 9 1 0 0 0 0 6 50 1 0 0 0 0 7 66 1 0 0 0 0 8 20 1 0 0 0 0 9 21 1 0 0 0 0 10 11 1 0 0 0 0 10 16 1 0 0 0 0 12 14 2 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 30 1 0 0 0 0 16 45 1 0 0 0 0 17 23 2 0 0 0 0 17 24 1 0 0 0 0 18 23 1 0 0 0 0 19 29 1 0 0 0 0 19 64 1 0 0 0 0 20 3 1 1 0 0 0 21 4 1 6 0 0 0 22 5 1 6 0 0 0 22 32 1 0 0 0 0 22 65 1 0 0 0 0 24 28 2 0 0 0 0 24 42 1 0 0 0 0 25 11 1 1 0 0 0 25 34 1 0 0 0 0 25 46 1 0 0 0 0 26 13 1 1 0 0 0 26 38 1 0 0 0 0 26 47 1 0 0 0 0 27 18 1 1 0 0 0 27 35 1 0 0 0 0 27 50 1 0 0 0 0 28 52 1 0 0 0 0 29 36 1 0 0 0 0 29 53 1 1 0 0 0 30 51 1 0 0 0 0 30 54 1 6 0 0 0 31 20 1 1 0 0 0 31 40 1 0 0 0 0 31 48 1 0 0 0 0 32 37 1 0 0 0 0 32 49 1 6 0 0 0 33 21 1 1 0 0 0 33 39 1 0 0 0 0 33 51 1 0 0 0 0 34 47 2 3 0 0 0 34 55 1 0 0 0 0 35 48 2 3 0 0 0 35 56 1 0 0 0 0 36 49 2 3 0 0 0 36 57 1 0 0 0 0 37 46 2 3 0 0 0 37 58 1 0 0 0 0 38 51 1 0 0 0 0 38 59 2 0 0 0 0 39 50 1 0 0 0 0 39 60 2 0 0 0 0 40 61 2 0 0 0 0 40 65 1 0 0 0 0 41 43 2 0 0 0 0 41 44 1 0 0 0 0 41 45 1 0 0 0 0 62 66 2 0 0 0 0 63 66 2 0 0 0 0 64 66 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	973.4
Volume:	918.776
LogP:	0.166
LogD:	0.071
LogS:	-2.129
# Rotatable Bonds:	17
TPSA:	349.28
# H-Bond Aceptor:	23
# H-Bond Donor:	11
# Rings:	3
# Heavy Atoms:	25

MedChem Properties

QED Drug-Likeness Score:	0.031
Synthetic Accessibility Score:	7.005
Fsp3:	0.659
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	1
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-6.842
MDCK Permeability:	5.8803020692721475e-06
Pgp-inhibitor:	0.021
Pgp-substrate:	1.0
Human Intestinal Absorption (HIA):	0.935
20% Bioavailability (F20%):	0.983
30% Bioavailability (F30%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.037
Plasma Protein Binding (PPB):	64.67346954345703%
Volume Distribution (VD):	0.326
Pgp-substrate:	23.82118797302246%

ADMET: Metabolism

CYP1A2-inhibitor:	0.0
CYP1A2-substrate:	0.009
CYP2C19-inhibitor:	0.024
CYP2C19-substrate:	0.035
CYP2C9-inhibitor:	0.083
CYP2C9-substrate:	0.019
CYP2D6-inhibitor:	0.002
CYP2D6-substrate:	0.058
CYP3A4-inhibitor:	0.05
CYP3A4-substrate:	0.017

ADMET: Excretion

Clearance (CL):	1.887
Half-life (T1/2):	0.33

ADMET: Toxicity

hERG Blockers:	0.058
Human Hepatotoxicity (H-HT):	0.761
Drug-inuced Liver Injury (DILI):	0.976
AMES Toxicity:	0.015
Rat Oral Acute Toxicity:	0.562
Maximum Recommended Daily Dose:	0.97
Skin Sensitization:	0.532
Carcinogencity:	0.238
Eye Corrosion:	0.003
Eye Irritation:	0.003
Respiratory Toxicity:	0.348

Download Data

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

Natural Product: NPC469444

Natural Product ID:	NPC469444
*Common Name:**	Micropeptin 478-A
IUPAC Name:	[(2R)-3-[[(2S,5S,8S,11R,12S,15S,18S,21R)-2,8-bis[(2S)-butan-2-yl]-5-[(3-chloro-4-hydroxyphenyl)methyl]-15-[3-(diaminomethylideneamino)propyl]-21-hydroxy-4,11-dimethyl-3,6,9,13,16,22-hexaoxo-10-oxa-1,4,7,14,17-pentazabicyclo[16.3.1]docosan-12-yl]amino]-2-hydroxy-3-oxopropyl] methanesulfonate
Synonyms:	Micropeptin 478 A
Standard InCHIKey:	QVGYFOADABRHJT-BYJMUUBVSA-N
Standard InCHI:	InChI=1S/C41H64ClN9O14S/c1-8-20(3)31-40(61)65-22(5)32(49-36(57)29(53)19-64-66(7,62)63)37(58)46-25(11-10-16-45-41(43)44)34(55)47-26-13-15-30(54)51(38(26)59)33(21(4)9-2)39(60)50(6)27(35(56)48-31)18-23-12-14-28(52)24(42)17-23/h12,14,17,20-22,25-27,29-33,52-54H,8-11,13,15-16,18-19H2,1-7H3,(H,46,58)(H,47,55)(H,48,56)(H,49,57)(H4,43,44,45)/t20-,21-,22+,25-,26-,27-,29+,30+,31-,32-,33-/m0/s1
SMILES:	CCC(C)C1C(=O)OC(C(C(=O)NC(C(=O)NC2CCC(N(C2=O)C(C(=O)N(C(C(=O)N1)CC3=CC(=C(C=C3)O)Cl)C)C(C)CC)O)CCCN=C(N)N)NC(=O)C(COS(=O)(=O)C)O)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1078917
PubChem CID:	46883093
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0001813] Peptidomimetics [CHEMONTID:0001961] Depsipeptides [CHEMONTID:0001994] Cyclic depsipeptides

*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
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	PMID[11000050]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	PMID[11374973]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	PMID[12141855]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	Einan Reservoir in Israel	n.a.	PMID[12141855]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	PMID[18163584]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	PMID[18558743]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	PMID[18973386]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	water bloom of the cyanobacterium Microcystis aeruginosa	n.a.	n.a.	PMID[19650639]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	bloom material	Lake Kinneret, Israel	n.a.	PMID[22280481]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	Kibbutz Geva, Israel	n.a.	PMID[23153007]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	Water Reservoir near Kibbutz Hafetz Haim, Israel	n.a.	PMID[23718637]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	Bloom	n.a.	n.a.	PMID[24261937]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	PMID[24642434]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	PMID[24868986]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	PMID[29405714]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	Bloom	n.a.	n.a.	PMID[29847132]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	PMID[9249979]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	PMID[9842728]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	Database[Title]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	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	3

Activity Type	# Activity
Individual Protein	1
Others	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1720	Individual Protein	Plasminogen	Homo sapiens	IC50	=	0.1	ug.mL-1	PMID[544079]
NPT2	Others	Unspecified		IC50	=	700.0	nM	PMID[544080]
NPT2	Others	Unspecified		IC50	=	5200.0	nM	PMID[544080]

☑ 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 NPC469444 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	220
0.1-0.2	1477
0.2-0.3	9667
0.3-0.4	10778
0.4-0.5	18273
0.5-0.6	1758
0.6-0.7	347
0.7-0.8	150
0.8-0.85	13
0.85-0.9	5
0.9-0.95	5
0.95-1	4

Similarity Score	Similarity Level	Natural Product ID
0.984	High Similarity	NPC469445
0.9626	High Similarity	NPC220060
0.962	High Similarity	NPC469443
0.9223	High Similarity	NPC469442
0.9223	High Similarity	NPC277306
0.9128	High Similarity	NPC25539
0.9115	High Similarity	NPC219350
0.9115	High Similarity	NPC194699
0.8871	High Similarity	NPC102959
0.8824	High Similarity	NPC60516
0.8684	High Similarity	NPC302715
0.8594	High Similarity	NPC473371
0.8548	High Similarity	NPC473404
0.8333	Intermediate Similarity	NPC51047
0.8238	Intermediate Similarity	NPC61332
0.8238	Intermediate Similarity	NPC240130
0.8118	Intermediate Similarity	NPC46009
0.8103	Intermediate Similarity	NPC470728
0.805	Intermediate Similarity	NPC477551
0.8042	Intermediate Similarity	NPC50016
0.804	Intermediate Similarity	NPC477552
0.804	Intermediate Similarity	NPC477550
0.8032	Intermediate Similarity	NPC273755
0.8	Intermediate Similarity	NPC22883
0.8	Intermediate Similarity	NPC5719
0.8	Intermediate Similarity	NPC210377
0.8	Intermediate Similarity	NPC217804
0.7958	Intermediate Similarity	NPC45037
0.7926	Intermediate Similarity	NPC475204
0.7926	Intermediate Similarity	NPC475123
0.7914	Intermediate Similarity	NPC63040
0.788	Intermediate Similarity	NPC1390
0.788	Intermediate Similarity	NPC62104
0.7876	Intermediate Similarity	NPC476321
0.7861	Intermediate Similarity	NPC15068
0.7842	Intermediate Similarity	NPC306804
0.7835	Intermediate Similarity	NPC471526
0.7801	Intermediate Similarity	NPC473354
0.7788	Intermediate Similarity	NPC295795
0.7737	Intermediate Similarity	NPC274198
0.7737	Intermediate Similarity	NPC198254
0.7725	Intermediate Similarity	NPC107938
0.7725	Intermediate Similarity	NPC294516
0.7711	Intermediate Similarity	NPC477638
0.7711	Intermediate Similarity	NPC477632
0.7704	Intermediate Similarity	NPC471048
0.7704	Intermediate Similarity	NPC471049
0.7704	Intermediate Similarity	NPC471050
0.7696	Intermediate Similarity	NPC230611
0.7688	Intermediate Similarity	NPC163961
0.7688	Intermediate Similarity	NPC473305
0.768	Intermediate Similarity	NPC269750
0.768	Intermediate Similarity	NPC194671
0.7677	Intermediate Similarity	NPC94862
0.7656	Intermediate Similarity	NPC137627
0.7644	Intermediate Similarity	NPC40234
0.7644	Intermediate Similarity	NPC276506
0.7641	Intermediate Similarity	NPC153554
0.7633	Intermediate Similarity	NPC81845
0.7617	Intermediate Similarity	NPC279871
0.7617	Intermediate Similarity	NPC26108
0.7617	Intermediate Similarity	NPC473402
0.7617	Intermediate Similarity	NPC471165
0.7614	Intermediate Similarity	NPC294951
0.7612	Intermediate Similarity	NPC477631
0.76	Intermediate Similarity	NPC477636
0.7598	Intermediate Similarity	NPC323662
0.7592	Intermediate Similarity	NPC280022
0.7577	Intermediate Similarity	NPC196243
0.7562	Intermediate Similarity	NPC473407
0.7562	Intermediate Similarity	NPC473378
0.7526	Intermediate Similarity	NPC155506
0.7526	Intermediate Similarity	NPC159767
0.7526	Intermediate Similarity	NPC476227
0.7524	Intermediate Similarity	NPC473450
0.7488	Intermediate Similarity	NPC328763
0.7474	Intermediate Similarity	NPC248670
0.7448	Intermediate Similarity	NPC209463
0.7435	Intermediate Similarity	NPC63931
0.7415	Intermediate Similarity	NPC477639
0.7411	Intermediate Similarity	NPC119652
0.7411	Intermediate Similarity	NPC97526
0.7409	Intermediate Similarity	NPC129486
0.7385	Intermediate Similarity	NPC475532
0.7368	Intermediate Similarity	NPC469243
0.7368	Intermediate Similarity	NPC471527
0.7358	Intermediate Similarity	NPC478005
0.7347	Intermediate Similarity	NPC165285
0.7347	Intermediate Similarity	NPC17698
0.734	Intermediate Similarity	NPC473580
0.7317	Intermediate Similarity	NPC65714
0.7304	Intermediate Similarity	NPC248822
0.7277	Intermediate Similarity	NPC475544
0.7254	Intermediate Similarity	NPC223207
0.725	Intermediate Similarity	NPC477637
0.7234	Intermediate Similarity	NPC473341
0.7227	Intermediate Similarity	NPC478007
0.7216	Intermediate Similarity	NPC304074
0.7216	Intermediate Similarity	NPC471771
0.7216	Intermediate Similarity	NPC290755
0.7212	Intermediate Similarity	NPC471592
0.72	Intermediate Similarity	NPC475409
0.72	Intermediate Similarity	NPC170302
0.72	Intermediate Similarity	NPC475564
0.7163	Intermediate Similarity	NPC329295
0.7162	Intermediate Similarity	NPC478008
0.7157	Intermediate Similarity	NPC89831
0.71	Intermediate Similarity	NPC473546
0.7073	Intermediate Similarity	NPC96275
0.7053	Intermediate Similarity	NPC262166
0.7041	Intermediate Similarity	NPC61004
0.7033	Intermediate Similarity	NPC80514
0.7032	Intermediate Similarity	NPC326027
0.7026	Intermediate Similarity	NPC471051
0.7026	Intermediate Similarity	NPC471053
0.7026	Intermediate Similarity	NPC471052
0.7018	Intermediate Similarity	NPC326333
0.7011	Intermediate Similarity	NPC239762
0.7011	Intermediate Similarity	NPC163392
0.7011	Intermediate Similarity	NPC48202
0.7005	Intermediate Similarity	NPC81026
0.7	Intermediate Similarity	NPC158277
0.6995	Remote Similarity	NPC326349
0.6995	Remote Similarity	NPC323336
0.6985	Remote Similarity	NPC328494
0.6979	Remote Similarity	NPC476268
0.6976	Remote Similarity	NPC299806
0.6952	Remote Similarity	NPC266741
0.6935	Remote Similarity	NPC168861
0.6935	Remote Similarity	NPC471568
0.6935	Remote Similarity	NPC473693
0.6935	Remote Similarity	NPC91953
0.6935	Remote Similarity	NPC196091
0.6927	Remote Similarity	NPC39431
0.6923	Remote Similarity	NPC114806
0.6919	Remote Similarity	NPC302597
0.6915	Remote Similarity	NPC227778
0.6911	Remote Similarity	NPC300443
0.6904	Remote Similarity	NPC472923
0.6891	Remote Similarity	NPC244509
0.6884	Remote Similarity	NPC66490
0.6884	Remote Similarity	NPC186617
0.6882	Remote Similarity	NPC197921
0.6875	Remote Similarity	NPC246591
0.6875	Remote Similarity	NPC56685
0.6872	Remote Similarity	NPC24617
0.6872	Remote Similarity	NPC244336
0.6845	Remote Similarity	NPC469360
0.6828	Remote Similarity	NPC214988
0.6825	Remote Similarity	NPC314083
0.6811	Remote Similarity	NPC6570
0.6806	Remote Similarity	NPC2501
0.6788	Remote Similarity	NPC5194
0.6788	Remote Similarity	NPC261934
0.6788	Remote Similarity	NPC122590
0.6771	Remote Similarity	NPC473491
0.6766	Remote Similarity	NPC151030
0.6766	Remote Similarity	NPC269383
0.675	Remote Similarity	NPC328649
0.6732	Remote Similarity	NPC475421
0.673	Remote Similarity	NPC477526
0.6702	Remote Similarity	NPC16188
0.6702	Remote Similarity	NPC311658
0.6701	Remote Similarity	NPC202198
0.6699	Remote Similarity	NPC134413
0.6699	Remote Similarity	NPC263507
0.6699	Remote Similarity	NPC271958
0.6699	Remote Similarity	NPC45112
0.6698	Remote Similarity	NPC477527
0.6684	Remote Similarity	NPC7817
0.6684	Remote Similarity	NPC475168
0.6667	Remote Similarity	NPC4910
0.6651	Remote Similarity	NPC315542
0.665	Remote Similarity	NPC297145
0.665	Remote Similarity	NPC197743
0.6649	Remote Similarity	NPC233702
0.6636	Remote Similarity	NPC184933
0.6636	Remote Similarity	NPC59827
0.6635	Remote Similarity	NPC167763
0.6635	Remote Similarity	NPC470112
0.6635	Remote Similarity	NPC470903
0.6633	Remote Similarity	NPC241794
0.6632	Remote Similarity	NPC52748
0.6631	Remote Similarity	NPC127741
0.6618	Remote Similarity	NPC49315
0.6614	Remote Similarity	NPC476989
0.6613	Remote Similarity	NPC267237
0.6604	Remote Similarity	NPC64140
0.6604	Remote Similarity	NPC174122
0.6588	Remote Similarity	NPC329731
0.6582	Remote Similarity	NPC470902
0.6571	Remote Similarity	NPC138083
0.6566	Remote Similarity	NPC324850
0.6557	Remote Similarity	NPC234069
0.6555	Remote Similarity	NPC86678
0.655	Remote Similarity	NPC73655
0.6535	Remote Similarity	NPC254700
0.6528	Remote Similarity	NPC135121
0.651	Remote Similarity	NPC477217
0.651	Remote Similarity	NPC315266

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 NPC469444 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	128
0.1-0.2	473
0.2-0.3	944
0.3-0.4	2214
0.4-0.5	3895
0.5-0.6	1417
0.6-0.7	76
0.7-0.8	3
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
0.7672	Intermediate Similarity	NPD8303	Discontinued
0.7225	Intermediate Similarity	NPD8019	Approved
0.7135	Intermediate Similarity	NPD7495	Discontinued
0.7053	Intermediate Similarity	NPD7523	Phase 3
0.6907	Remote Similarity	NPD7118	Clinical (unspecified phase)
0.6755	Remote Similarity	NPD8076	Discontinued
0.6746	Remote Similarity	NPD6089	Clinical (unspecified phase)
0.6736	Remote Similarity	NPD7303	Discontinued
0.6736	Remote Similarity	NPD6689	Clinical (unspecified phase)
0.6699	Remote Similarity	NPD7959	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD8014	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD7978	Discontinued
0.6651	Remote Similarity	NPD5946	Clinical (unspecified phase)
0.6649	Remote Similarity	NPD6078	Clinical (unspecified phase)
0.6634	Remote Similarity	NPD7485	Phase 3
0.6634	Remote Similarity	NPD7484	Phase 3
0.6632	Remote Similarity	NPD5341	Clinical (unspecified phase)
0.663	Remote Similarity	NPD3136	Phase 2
0.6601	Remote Similarity	NPD7608	Discontinued
0.6583	Remote Similarity	NPD3465	Clinical (unspecified phase)
0.6582	Remote Similarity	NPD6670	Clinical (unspecified phase)
0.6558	Remote Similarity	NPD6312	Discontinued
0.6546	Remote Similarity	NPD6682	Clinical (unspecified phase)
0.6533	Remote Similarity	NPD4018	Clinical (unspecified phase)
0.6526	Remote Similarity	NPD7617	Discontinued
0.652	Remote Similarity	NPD4652	Approved
0.6513	Remote Similarity	NPD5348	Clinical (unspecified phase)
0.6505	Remote Similarity	NPD5200	Clinical (unspecified phase)
0.6485	Remote Similarity	NPD2098	Approved
0.648	Remote Similarity	NPD4731	Phase 3
0.6476	Remote Similarity	NPD3936	Clinical (unspecified phase)
0.6458	Remote Similarity	NPD6681	Discovery
0.645	Remote Similarity	NPD5356	Approved
0.645	Remote Similarity	NPD5355	Approved
0.6421	Remote Similarity	NPD6901	Phase 3
0.6415	Remote Similarity	NPD6851	Approved
0.6415	Remote Similarity	NPD6853	Approved
0.641	Remote Similarity	NPD4588	Clinical (unspecified phase)
0.641	Remote Similarity	NPD5308	Clinical (unspecified phase)
0.6404	Remote Similarity	NPD8031	Discontinued
0.639	Remote Similarity	NPD2890	Approved
0.639	Remote Similarity	NPD2017	Approved
0.639	Remote Similarity	NPD2888	Approved
0.639	Remote Similarity	NPD2889	Approved
0.6387	Remote Similarity	NPD6867	Clinical (unspecified phase)
0.6387	Remote Similarity	NPD6866	Clinical (unspecified phase)
0.6386	Remote Similarity	NPD2097	Approved
0.6379	Remote Similarity	NPD6796	Discontinued
0.6373	Remote Similarity	NPD6119	Clinical (unspecified phase)
0.6359	Remote Similarity	NPD5309	Clinical (unspecified phase)
0.6351	Remote Similarity	NPD4971	Clinical (unspecified phase)
0.6323	Remote Similarity	NPD5152	Clinical (unspecified phase)
0.6308	Remote Similarity	NPD7066	Clinical (unspecified phase)
0.6286	Remote Similarity	NPD5096	Phase 3
0.6286	Remote Similarity	NPD3933	Discontinued
0.6286	Remote Similarity	NPD5095	Phase 3
0.6283	Remote Similarity	NPD4782	Clinical (unspecified phase)
0.6281	Remote Similarity	NPD7131	Phase 3
0.6279	Remote Similarity	NPD3857	Clinical (unspecified phase)
0.6278	Remote Similarity	NPD8162	Phase 2
0.6278	Remote Similarity	NPD8163	Clinical (unspecified phase)
0.6263	Remote Similarity	NPD6419	Discontinued
0.625	Remote Similarity	NPD5137	Approved
0.6244	Remote Similarity	NPD8290	Clinical (unspecified phase)
0.6244	Remote Similarity	NPD5219	Approved
0.6244	Remote Similarity	NPD5218	Approved
0.6237	Remote Similarity	NPD6809	Clinical (unspecified phase)
0.623	Remote Similarity	NPD4757	Clinical (unspecified phase)
0.6227	Remote Similarity	NPD3659	Discontinued
0.6226	Remote Similarity	NPD6297	Approved
0.6216	Remote Similarity	NPD7811	Phase 3
0.6216	Remote Similarity	NPD7810	Phase 3
0.6211	Remote Similarity	NPD5729	Clinical (unspecified phase)
0.6186	Remote Similarity	NPD7450	Phase 2
0.6165	Remote Similarity	NPD4521	Clinical (unspecified phase)
0.6161	Remote Similarity	NPD6256	Approved
0.6161	Remote Similarity	NPD6255	Approved
0.6161	Remote Similarity	NPD6254	Approved
0.6158	Remote Similarity	NPD2541	Clinical (unspecified phase)
0.6158	Remote Similarity	NPD7749	Clinical (unspecified phase)
0.6157	Remote Similarity	NPD3803	Clinical (unspecified phase)
0.6126	Remote Similarity	NPD829	Discontinued
0.6123	Remote Similarity	NPD6905	Phase 2
0.6119	Remote Similarity	NPD6058	Phase 2
0.6116	Remote Similarity	NPD6253	Approved
0.6111	Remote Similarity	NPD6237	Clinical (unspecified phase)
0.6109	Remote Similarity	NPD8292	Phase 2
0.6094	Remote Similarity	NPD4791	Clinical (unspecified phase)
0.6073	Remote Similarity	NPD1330	Phase 2
0.6073	Remote Similarity	NPD1329	Clinical (unspecified phase)
0.6061	Remote Similarity	NPD1968	Approved
0.6061	Remote Similarity	NPD1967	Approved
0.6059	Remote Similarity	NPD6056	Approved
0.6059	Remote Similarity	NPD6057	Approved
0.605	Remote Similarity	NPD6088	Approved
0.6031	Remote Similarity	NPD8172	Phase 2
0.6031	Remote Similarity	NPD8173	Phase 2
0.6031	Remote Similarity	NPD6073	Approved
0.603	Remote Similarity	NPD8323	Discontinued
0.6027	Remote Similarity	NPD4157	Discontinued
0.602	Remote Similarity	NPD3536	Discontinued
0.6019	Remote Similarity	NPD7132	Clinical (unspecified phase)
0.6011	Remote Similarity	NPD3125	Approved
0.601	Remote Similarity	NPD7836	Clinical (unspecified phase)
0.601	Remote Similarity	NPD2976	Clinical (unspecified phase)
0.601	Remote Similarity	NPD5296	Approved
0.6	Remote Similarity	NPD4177	Approved
0.6	Remote Similarity	NPD4175	Approved
0.5991	Remote Similarity	NPD6863	Phase 2
0.599	Remote Similarity	NPD3632	Clinical (unspecified phase)
0.599	Remote Similarity	NPD6390	Discontinued
0.599	Remote Similarity	NPD6646	Discontinued
0.5984	Remote Similarity	NPD7963	Phase 3
0.5982	Remote Similarity	NPD5872	Discontinued
0.5979	Remote Similarity	NPD555	Phase 2
0.5975	Remote Similarity	NPD4086	Phase 1
0.5973	Remote Similarity	NPD3602	Clinical (unspecified phase)
0.5972	Remote Similarity	NPD5192	Clinical (unspecified phase)
0.5966	Remote Similarity	NPD3879	Approved
0.5959	Remote Similarity	NPD5745	Approved
0.5951	Remote Similarity	NPD8417	Discontinued
0.5949	Remote Similarity	NPD5725	Approved
0.5942	Remote Similarity	NPD4557	Approved
0.594	Remote Similarity	NPD6189	Approved
0.594	Remote Similarity	NPD6188	Approved
0.5939	Remote Similarity	NPD2239	Approved
0.5939	Remote Similarity	NPD3175	Clinical (unspecified phase)
0.5939	Remote Similarity	NPD2240	Approved
0.5938	Remote Similarity	NPD6919	Clinical (unspecified phase)
0.5931	Remote Similarity	NPD1972	Approved
0.5931	Remote Similarity	NPD1969	Clinical (unspecified phase)
0.5931	Remote Similarity	NPD1973	Approved
0.593	Remote Similarity	NPD6860	Clinical (unspecified phase)
0.5923	Remote Similarity	NPD3878	Approved
0.5918	Remote Similarity	NPD3554	Approved
0.5918	Remote Similarity	NPD6852	Discontinued
0.5918	Remote Similarity	NPD3552	Approved
0.5918	Remote Similarity	NPD3555	Approved
0.5918	Remote Similarity	NPD3553	Approved
0.5911	Remote Similarity	NPD7613	Discontinued
0.5911	Remote Similarity	NPD4186	Clinical (unspecified phase)
0.5907	Remote Similarity	NPD2078	Clinical (unspecified phase)
0.5904	Remote Similarity	NPD2562	Approved
0.5904	Remote Similarity	NPD2561	Approved
0.5903	Remote Similarity	NPD5542	Phase 2
0.5897	Remote Similarity	NPD6187	Approved
0.5895	Remote Similarity	NPD2585	Clinical (unspecified phase)
0.5891	Remote Similarity	NPD5614	Approved
0.5891	Remote Similarity	NPD5613	Approved
0.5888	Remote Similarity	NPD3366	Approved
0.5882	Remote Similarity	NPD2854	Approved
0.5882	Remote Similarity	NPD2856	Approved
0.5882	Remote Similarity	NPD2855	Approved
0.5882	Remote Similarity	NPD8025	Phase 2
0.588	Remote Similarity	NPD7574	Phase 2
0.5876	Remote Similarity	NPD5747	Discontinued
0.5876	Remote Similarity	NPD259	Phase 1
0.5874	Remote Similarity	NPD2891	Approved
0.5867	Remote Similarity	NPD823	Approved
0.5867	Remote Similarity	NPD817	Approved
0.5867	Remote Similarity	NPD2568	Approved
0.5867	Remote Similarity	NPD5314	Approved
0.5865	Remote Similarity	NPD7972	Discontinued
0.5865	Remote Similarity	NPD4567	Approved
0.5865	Remote Similarity	NPD4566	Approved
0.5864	Remote Similarity	NPD5339	Clinical (unspecified phase)
0.586	Remote Similarity	NPD8022	Clinical (unspecified phase)
0.5855	Remote Similarity	NPD5746	Approved
0.585	Remote Similarity	NPD5265	Approved
0.585	Remote Similarity	NPD5264	Approved
0.5849	Remote Similarity	NPD6107	Approved
0.5848	Remote Similarity	NPD7429	Clinical (unspecified phase)
0.5846	Remote Similarity	NPD4153	Approved
0.5846	Remote Similarity	NPD6346	Approved
0.5842	Remote Similarity	NPD3098	Discontinued
0.5841	Remote Similarity	NPD7282	Approved
0.5838	Remote Similarity	NPD6295	Approved
0.5838	Remote Similarity	NPD6294	Approved
0.5837	Remote Similarity	NPD5967	Approved
0.5833	Remote Similarity	NPD4914	Approved
0.5833	Remote Similarity	NPD7805	Phase 3
0.5825	Remote Similarity	NPD597	Approved
0.5825	Remote Similarity	NPD3455	Phase 2
0.5825	Remote Similarity	NPD601	Approved
0.5825	Remote Similarity	NPD598	Approved
0.5821	Remote Similarity	NPD6676	Phase 2
0.5819	Remote Similarity	NPD8066	Clinical (unspecified phase)
0.5817	Remote Similarity	NPD2515	Approved
0.5817	Remote Similarity	NPD3007	Approved
0.5811	Remote Similarity	NPD779	Phase 2
0.581	Remote Similarity	NPD4565	Clinical (unspecified phase)
0.581	Remote Similarity	NPD4564	Clinical (unspecified phase)
0.5809	Remote Similarity	NPD8356	Approved
0.5808	Remote Similarity	NPD5301	Clinical (unspecified phase)
0.5806	Remote Similarity	NPD5774	Approved
0.5806	Remote Similarity	NPD5775	Approved
0.5806	Remote Similarity	NPD7695	Clinical (unspecified phase)
0.5806	Remote Similarity	NPD5485	Approved
0.5806	Remote Similarity	NPD5484	Approved
0.5806	Remote Similarity	NPD2218	Phase 2

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