Structure

Physi-Chem Properties

Molecular Weight:  255.18
Volume:  268.318
LogP:  1.306
LogD:  0.421
LogS:  -0.632
# Rotatable Bonds:  6
TPSA:  49.77
# H-Bond Aceptor:  4
# H-Bond Donor:  1
# Rings:  2
# Heavy Atoms:  4

MedChem Properties

QED Drug-Likeness Score:  0.729
Synthetic Accessibility Score:  3.996
Fsp3:  0.929
Lipinski Rule-of-5:  Accepted
Pfizer Rule:  Accepted
GSK Rule:  Accepted
BMS Rule:  1
Golden Triangle Rule:  Accepted
Chelating Alert:  0
PAINS Alert:  0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:  -4.64
MDCK Permeability:  1.574399539094884e-05
Pgp-inhibitor:  0.005
Pgp-substrate:  0.139
Human Intestinal Absorption (HIA):  0.007
20% Bioavailability (F20%):  0.017
30% Bioavailability (F30%):  0.015

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.925
Plasma Protein Binding (PPB):  48.006858825683594%
Volume Distribution (VD):  2.946
Pgp-substrate:  63.42656707763672%

ADMET: Metabolism

CYP1A2-inhibitor:  0.023
CYP1A2-substrate:  0.104
CYP2C19-inhibitor:  0.019
CYP2C19-substrate:  0.894
CYP2C9-inhibitor:  0.001
CYP2C9-substrate:  0.061
CYP2D6-inhibitor:  0.409
CYP2D6-substrate:  0.657
CYP3A4-inhibitor:  0.004
CYP3A4-substrate:  0.47

ADMET: Excretion

Clearance (CL):  6.392
Half-life (T1/2):  0.817

ADMET: Toxicity

hERG Blockers:  0.042
Human Hepatotoxicity (H-HT):  0.56
Drug-inuced Liver Injury (DILI):  0.274
AMES Toxicity:  0.107
Rat Oral Acute Toxicity:  0.369
Maximum Recommended Daily Dose:  0.167
Skin Sensitization:  0.555
Carcinogencity:  0.629
Eye Corrosion:  0.093
Eye Irritation:  0.585
Respiratory Toxicity:  0.809

Download Data

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

  Natural Product: NPC233108

Natural Product ID:  NPC233108
Common Name*:   Cremastrine
IUPAC Name:   [(1S,8S)-2,3,5,6,7,8-hexahydro-1H-pyrrolizin-1-yl]methyl (2R,3R)-2-hydroxy-3-methylpentanoate
Synonyms:   Cremastrine
Standard InCHIKey:  AVBKRVFZNFJQBK-FVCCEPFGSA-N
Standard InCHI:  InChI=1S/C14H25NO3/c1-3-10(2)13(16)14(17)18-9-11-6-8-15-7-4-5-12(11)15/h10-13,16H,3-9H2,1-2H3/t10-,11-,12+,13-/m1/s1
SMILES:  CC[C@H]([C@H](C(=O)OC[C@H]1CCN2[C@H]1CCC2)O)C
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL480464
PubChem CID:   656392
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000220] Pyrrolizidines

*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
NPO1756 Cremastra appendiculata Species Orchidaceae Eukaryota n.a. bulb n.a. PMID[14994197]
NPO1756 Cremastra appendiculata Species Orchidaceae Eukaryota n.a. n.a. n.a. PMID[15844951]
NPO1756 Cremastra appendiculata Species Orchidaceae Eukaryota tubers n.a. n.a. PMID[16792409]
NPO1756 Cremastra appendiculata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1756 Cremastra appendiculata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1756 Cremastra appendiculata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO1756 Cremastra appendiculata Species Orchidaceae 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

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT262 Individual Protein Muscarinic acetylcholine receptor M1 Homo sapiens IC50 = 505.0 nM PMID[500728]
NPT263 Individual Protein Muscarinic acetylcholine receptor M2 Homo sapiens IC50 > 5517.0 nM PMID[500728]
NPT264 Individual Protein Muscarinic acetylcholine receptor M3 Homo sapiens IC50 = 126.0 nM PMID[500728]
NPT265 Individual Protein Muscarinic acetylcholine receptor M4 Homo sapiens IC50 = 498.0 nM PMID[500728]
NPT266 Individual Protein Muscarinic acetylcholine receptor M5 Homo sapiens IC50 = 1220.0 nM PMID[500728]

☑ 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 NPC233108 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.56 or Top200).

Similarity Score Similarity Level Natural Product ID
0.8537 High Similarity NPC52533
0.7033 Intermediate Similarity NPC476019
0.6941 Remote Similarity NPC216090
0.6932 Remote Similarity NPC277918
0.6667 Remote Similarity NPC319991
0.663 Remote Similarity NPC322966
0.663 Remote Similarity NPC203170
0.6625 Remote Similarity NPC171850
0.66 Remote Similarity NPC279833
0.66 Remote Similarity NPC80439
0.66 Remote Similarity NPC173690
0.6575 Remote Similarity NPC471442
0.6575 Remote Similarity NPC471423
0.6574 Remote Similarity NPC235625
0.6543 Remote Similarity NPC475127
0.6543 Remote Similarity NPC473419
0.6543 Remote Similarity NPC475715
0.6535 Remote Similarity NPC64168
0.65 Remote Similarity NPC59221
0.6471 Remote Similarity NPC471844
0.6436 Remote Similarity NPC6271
0.642 Remote Similarity NPC474469
0.642 Remote Similarity NPC254617
0.642 Remote Similarity NPC74555
0.642 Remote Similarity NPC306763
0.642 Remote Similarity NPC266242
0.64 Remote Similarity NPC471605
0.64 Remote Similarity NPC471443
0.6389 Remote Similarity NPC39041
0.6389 Remote Similarity NPC471845
0.6389 Remote Similarity NPC241294
0.6389 Remote Similarity NPC202722
0.6389 Remote Similarity NPC471846
0.6296 Remote Similarity NPC184150
0.6296 Remote Similarity NPC141156
0.6265 Remote Similarity NPC115800
0.6265 Remote Similarity NPC163538
0.625 Remote Similarity NPC160661
0.625 Remote Similarity NPC173763
0.625 Remote Similarity NPC62263
0.625 Remote Similarity NPC471098
0.6211 Remote Similarity NPC474593
0.6211 Remote Similarity NPC475801
0.6204 Remote Similarity NPC63191
0.6204 Remote Similarity NPC471202
0.62 Remote Similarity NPC220234
0.6186 Remote Similarity NPC469998
0.6173 Remote Similarity NPC12514
0.6173 Remote Similarity NPC294883
0.6168 Remote Similarity NPC30911
0.6168 Remote Similarity NPC316984
0.6146 Remote Similarity NPC474576
0.6136 Remote Similarity NPC473741
0.6136 Remote Similarity NPC477145
0.6125 Remote Similarity NPC57420
0.6117 Remote Similarity NPC265094
0.6095 Remote Similarity NPC271562
0.6087 Remote Similarity NPC320936
0.6055 Remote Similarity NPC130124
0.6055 Remote Similarity NPC193471
0.6049 Remote Similarity NPC472609
0.6034 Remote Similarity NPC474371
0.6023 Remote Similarity NPC330017
0.6019 Remote Similarity NPC301148
0.6019 Remote Similarity NPC5864
0.6019 Remote Similarity NPC124554
0.6 Remote Similarity NPC471843
0.6 Remote Similarity NPC160066
0.6 Remote Similarity NPC474702
0.6 Remote Similarity NPC178263
0.6 Remote Similarity NPC277072
0.5982 Remote Similarity NPC201889
0.5982 Remote Similarity NPC106791
0.5974 Remote Similarity NPC293551
0.5962 Remote Similarity NPC471260
0.5905 Remote Similarity NPC124549
0.5889 Remote Similarity NPC473984
0.5888 Remote Similarity NPC67009
0.5882 Remote Similarity NPC476291
0.5882 Remote Similarity NPC478256
0.5882 Remote Similarity NPC476285
0.5877 Remote Similarity NPC11379
0.5872 Remote Similarity NPC168758
0.5872 Remote Similarity NPC47857
0.5872 Remote Similarity NPC181510
0.5862 Remote Similarity NPC475260
0.5862 Remote Similarity NPC473699
0.5862 Remote Similarity NPC263281
0.5862 Remote Similarity NPC474100
0.5862 Remote Similarity NPC473775
0.5862 Remote Similarity NPC178919
0.5862 Remote Similarity NPC51249
0.5862 Remote Similarity NPC475232
0.5854 Remote Similarity NPC233034
0.5843 Remote Similarity NPC472594
0.5841 Remote Similarity NPC284656
0.5826 Remote Similarity NPC23963
0.581 Remote Similarity NPC198344
0.5794 Remote Similarity NPC137453
0.5773 Remote Similarity NPC292345
0.5769 Remote Similarity NPC188785
0.5765 Remote Similarity NPC82315
0.5765 Remote Similarity NPC15864
0.5761 Remote Similarity NPC470783
0.5758 Remote Similarity NPC315237
0.575 Remote Similarity NPC470363
0.5747 Remote Similarity NPC29326
0.5743 Remote Similarity NPC150041
0.5741 Remote Similarity NPC171734
0.5732 Remote Similarity NPC471419
0.5732 Remote Similarity NPC163134
0.573 Remote Similarity NPC228411
0.573 Remote Similarity NPC476324
0.573 Remote Similarity NPC476130
0.5728 Remote Similarity NPC475440
0.5726 Remote Similarity NPC471255
0.5714 Remote Similarity NPC78312
0.5714 Remote Similarity NPC227622
0.5714 Remote Similarity NPC221764
0.5714 Remote Similarity NPC194750
0.5714 Remote Similarity NPC233274
0.5714 Remote Similarity NPC287638
0.5714 Remote Similarity NPC135539
0.5714 Remote Similarity NPC196359
0.5701 Remote Similarity NPC475637
0.5699 Remote Similarity NPC246005
0.5696 Remote Similarity NPC190385
0.5686 Remote Similarity NPC313821
0.5682 Remote Similarity NPC43219
0.5682 Remote Similarity NPC138435
0.5679 Remote Similarity NPC477644
0.567 Remote Similarity NPC304454
0.5663 Remote Similarity NPC314103
0.5658 Remote Similarity NPC471607
0.5647 Remote Similarity NPC469925
0.5647 Remote Similarity NPC34291
0.5647 Remote Similarity NPC126664
0.5634 Remote Similarity NPC319680
0.5632 Remote Similarity NPC33267
0.5632 Remote Similarity NPC324165
0.5632 Remote Similarity NPC170963
0.5632 Remote Similarity NPC126366
0.5632 Remote Similarity NPC114640
0.5632 Remote Similarity NPC169976
0.5631 Remote Similarity NPC476344
0.5625 Remote Similarity NPC469363
0.5618 Remote Similarity NPC327272
0.5618 Remote Similarity NPC86064
0.5618 Remote Similarity NPC472595
0.5614 Remote Similarity NPC65045
0.561 Remote Similarity NPC17455
0.5607 Remote Similarity NPC323720
0.5604 Remote Similarity NPC316242
0.56 Remote Similarity NPC208537
0.56 Remote Similarity NPC270005

  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 NPC233108 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
0.7532 Intermediate Similarity NPD2695 Approved
0.7532 Intermediate Similarity NPD2697 Approved
0.7532 Intermediate Similarity NPD2696 Approved
0.7532 Intermediate Similarity NPD2694 Approved
0.6897 Remote Similarity NPD883 Phase 2
0.6897 Remote Similarity NPD882 Phase 2
0.6168 Remote Similarity NPD2204 Approved
0.6024 Remote Similarity NPD9444 Discontinued
0.6 Remote Similarity NPD7916 Approved
0.6 Remote Similarity NPD7915 Approved
0.5943 Remote Similarity NPD8140 Approved
0.593 Remote Similarity NPD6704 Discontinued
0.5909 Remote Similarity NPD1453 Phase 1
0.587 Remote Similarity NPD1448 Clinical (unspecified phase)
0.5854 Remote Similarity NPD9440 Discontinued
0.5854 Remote Similarity NPD1457 Discontinued
0.5843 Remote Similarity NPD2689 Clinical (unspecified phase)
0.5802 Remote Similarity NPD1146 Phase 2
0.5802 Remote Similarity NPD9676 Phase 3
0.5794 Remote Similarity NPD8307 Discontinued
0.5773 Remote Similarity NPD618 Clinical (unspecified phase)
0.573 Remote Similarity NPD376 Approved
0.573 Remote Similarity NPD11 Approved
0.5714 Remote Similarity NPD8082 Approved
0.5714 Remote Similarity NPD617 Approved
0.5714 Remote Similarity NPD8086 Approved
0.5714 Remote Similarity NPD8085 Approved
0.5714 Remote Similarity NPD8084 Approved
0.5714 Remote Similarity NPD8083 Approved
0.5714 Remote Similarity NPD8138 Approved
0.5714 Remote Similarity NPD8868 Approved
0.5714 Remote Similarity NPD8139 Approved
0.57 Remote Similarity NPD5781 Clinical (unspecified phase)
0.5698 Remote Similarity NPD2220 Clinical (unspecified phase)
0.5696 Remote Similarity NPD9023 Clinical (unspecified phase)
0.5686 Remote Similarity NPD3189 Approved
0.5686 Remote Similarity NPD3191 Approved
0.5686 Remote Similarity NPD3190 Approved
0.5682 Remote Similarity NPD355 Phase 2
0.5679 Remote Similarity NPD393 Approved
0.5663 Remote Similarity NPD4272 Discontinued
0.566 Remote Similarity NPD8276 Approved
0.566 Remote Similarity NPD8275 Approved
0.5647 Remote Similarity NPD9443 Clinical (unspecified phase)
0.5641 Remote Similarity NPD9454 Approved
0.5636 Remote Similarity NPD8087 Discontinued
0.5631 Remote Similarity NPD8038 Phase 2
0.5631 Remote Similarity NPD3714 Approved
0.5631 Remote Similarity NPD3715 Approved
0.5631 Remote Similarity NPD3713 Approved
0.5607 Remote Similarity NPD8081 Approved
0.5604 Remote Similarity NPD3160 Suspended

  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